Journal articles on the topic 'Chaperones'
To see the other types of publications on this topic, follow the link: Chaperones.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Chaperones.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Large, Andrew T., Martin D. Goldberg, and Peter A. Lund. "Chaperones and protein folding in the archaea." Biochemical Society Transactions 37, no. 1 (January 20, 2009): 46–51. http://dx.doi.org/10.1042/bst0370046.
Full textAbstract:
A survey of archaeal genomes for the presence of homologues of bacterial and eukaryotic chaperones reveals several interesting features. All archaea contain chaperonins, also known as Hsp60s (where Hsp is heat-shock protein). These are more similar to the type II chaperonins found in the eukaryotic cytosol than to the type I chaperonins found in bacteria, mitochondria and chloroplasts, although some archaea also contain type I chaperonin homologues, presumably acquired by horizontal gene transfer. Most archaea contain several genes for these proteins. Our studies on the type II chaperonins of the genetically tractable archaeon Haloferax volcanii have shown that only one of the three genes has to be present for the organisms to grow, but that there is some evidence for functional specialization between the different chaperonin proteins. All archaea also possess genes for prefoldin proteins and for small heat-shock proteins, but they generally lack genes for Hsp90 and Hsp100 homologues. Genes for Hsp70 (DnaK) and Hsp40 (DnaJ) homologues are only found in a subset of archaea. Thus chaperone-assisted protein folding in archaea is likely to display some unique features when compared with that in eukaryotes and bacteria, and there may be important differences in the process between euryarchaea and crenarchaea.
2
Hervás, Rubén, and Javier Oroz. "Mechanistic Insights into the Role of Molecular Chaperones in Protein Misfolding Diseases: From Molecular Recognition to Amyloid Disassembly." International Journal of Molecular Sciences 21, no. 23 (December 2, 2020): 9186. http://dx.doi.org/10.3390/ijms21239186.
Full textAbstract:
Age-dependent alterations in the proteostasis network are crucial in the progress of prevalent neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, or amyotrophic lateral sclerosis, which are characterized by the presence of insoluble protein deposits in degenerating neurons. Because molecular chaperones deter misfolded protein aggregation, regulate functional phase separation, and even dissolve noxious aggregates, they are considered major sentinels impeding the molecular processes that lead to cell damage in the course of these diseases. Indeed, members of the chaperome, such as molecular chaperones and co-chaperones, are increasingly recognized as therapeutic targets for the development of treatments against degenerative proteinopathies. Chaperones must recognize diverse toxic clients of different orders (soluble proteins, biomolecular condensates, organized protein aggregates). It is therefore critical to understand the basis of the selective chaperone recognition to discern the mechanisms of action of chaperones in protein conformational diseases. This review aimed to define the selective interplay between chaperones and toxic client proteins and the basis for the protective role of these interactions. The presence and availability of chaperone recognition motifs in soluble proteins and in insoluble aggregates, both functional and pathogenic, are discussed. Finally, the formation of aberrant (pro-toxic) chaperone complexes will also be disclosed.
3
Scalia, Federica, Alessandra Maria Vitale, Radha Santonocito, Everly Conway de Macario, Alberto J. L. Macario, and Francesco Cappello. "The Neurochaperonopathies: Anomalies of the Chaperone System with Pathogenic Effects in Neurodegenerative and Neuromuscular Disorders." Applied Sciences 11, no. 3 (January 20, 2021): 898. http://dx.doi.org/10.3390/app11030898.
Full textAbstract:
The chaperone (or chaperoning) system (CS) constitutes molecular chaperones, co-chaperones, and chaperone co-factors, interactors and receptors, and its canonical role is protein quality control. A malfunction of the CS may cause diseases, known as the chaperonopathies. These are caused by qualitatively and/or quantitatively abnormal molecular chaperones. Since the CS is ubiquitous, chaperonopathies are systemic, affecting various tissues and organs, playing an etiologic-pathogenic role in diverse conditions. In this review, we focus on chaperonopathies involved in the pathogenic mechanisms of diseases of the central and peripheral nervous systems: the neurochaperonopathies (NCPs). Genetic NCPs are linked to pathogenic variants of chaperone genes encoding, for example, the small Hsp, Hsp10, Hsp40, Hsp60, and CCT-BBS (chaperonin-containing TCP-1- Bardet–Biedl syndrome) chaperones. Instead, the acquired NCPs are associated with malfunctional chaperones, such as Hsp70, Hsp90, and VCP/p97 with aberrant post-translational modifications. Awareness of the chaperonopathies as the underlying primary or secondary causes of disease will improve diagnosis and patient management and open the possibility of investigating and developing chaperonotherapy, namely treatment with the abnormal chaperone as the main target. Positive chaperonotherapy would apply in chaperonopathies by defect, i.e., chaperone insufficiency, and consist of chaperone replacement or boosting, whereas negative chaperonotherapy would be pertinent when a chaperone actively participates in the initiation and progression of the disease and must be blocked and eliminated.
4
Scalia, Federica, Antonella Marino Gammazza, Everly Conway de Macario, Alberto J. L. Macario, and Francesco Cappello. "Myelin Pathology: Involvement of Molecular Chaperones and the Promise of Chaperonotherapy." Brain Sciences 9, no. 11 (October 30, 2019): 297. http://dx.doi.org/10.3390/brainsci9110297.
Full textAbstract:
The process of axon myelination involves various proteins including molecular chaperones. Myelin alteration is a common feature in neurological diseases due to structural and functional abnormalities of one or more myelin proteins. Genetic proteinopathies may occur either in the presence of a normal chaperoning system, which is unable to assist the defective myelin protein in its folding and migration, or due to mutations in chaperone genes, leading to functional defects in assisting myelin maturation/migration. The latter are a subgroup of genetic chaperonopathies causing demyelination. In this brief review, we describe some paradigmatic examples pertaining to the chaperonins Hsp60 (HSPD1, or HSP60, or Cpn60) and CCT (chaperonin-containing TCP-1). Our aim is to make scientists and physicians aware of the possibility and advantages of classifying patients depending on the presence or absence of a chaperonopathy. In turn, this subclassification will allow the development of novel therapeutic strategies (chaperonotherapy) by using molecular chaperones as agents or targets for treatment.
5
Wang, Lisha, Liza Bergkvist, Rajnish Kumar, Bengt Winblad, and Pavel F. Pavlov. "Targeting Chaperone/Co-Chaperone Interactions with Small Molecules: A Novel Approach to Tackle Neurodegenerative Diseases." Cells 10, no. 10 (September 29, 2021): 2596. http://dx.doi.org/10.3390/cells10102596.
Full textAbstract:
The dysfunction of the proteostasis network is a molecular hallmark of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Molecular chaperones are a major component of the proteostasis network and maintain cellular homeostasis by folding client proteins, assisting with intracellular transport, and interfering with protein aggregation or degradation. Heat shock protein 70 kDa (Hsp70) and 90 kDa (Hsp90) are two of the most important chaperones whose functions are dependent on ATP hydrolysis and collaboration with their co-chaperones. Numerous studies implicate Hsp70, Hsp90, and their co-chaperones in neurodegenerative diseases. Targeting the specific protein–protein interactions between chaperones and their particular partner co-chaperones with small molecules provides an opportunity to specifically modulate Hsp70 or Hsp90 function for neurodegenerative diseases. Here, we review the roles of co-chaperones in Hsp70 or Hsp90 chaperone cycles, the impacts of co-chaperones in neurodegenerative diseases, and the development of small molecules modulating chaperone/co-chaperone interactions. We also provide a future perspective of drug development targeting chaperone/co-chaperone interactions for neurodegenerative diseases.
6
Zahn, Ralph. "Prion propagation and molecular chaperones." Quarterly Reviews of Biophysics 32, no. 4 (November 1999): 309–70. http://dx.doi.org/10.1017/s0033583500003553.
Full textAbstract:
1. Introduction 3102. Protein-only hypothesis 3123. The scrapie prion protein PrPSc3133.1 Purification of PrP 27–30 3133.2 Proteinase K resistance 3143.3 Scrapie-associated fibrils 3143.4 Smallest infectious unit 3163.5 Conformational properties 3163.6 Dissociation and stability 3194. The cellular prion protein PrPC3214.1 Prnp expression 3214.2 Biosynthetic pathway 3224.3 NMR structures 3244.4 Copper binding 3265. Post-translational PrP conversion 3275.1 Conformational isoforms 3275.2 Location of propagation 3295.3 Minimal PrP sequence 3305.4 Prion species barrier 3315.5 Prion strains 3326. Effect of familial TSE mutations 3336.1 Thermodynamic stability of PrPC 3346.2 De novo synthesis of PrPSc 3356.3 Transmembrane PrP forms 3377. Physical properties of synthetic PrP 3377.1 Amyloidogenic peptides 3377.2 Folding intermediates 3398. Hypothetical protein X 3408.1 Two species-specific epitopes 3408.2 Mapping the protein X epitope 3419. Chaperone-mediated PrP conversion 3439.1 Hsp60 and Hsp10 chaperonins 3439.2 GroEL promoted PrP-res formation 3459.3 Membrane-associated chaperonins 3459.4 Preference of GroEL for positive charges 3479.5 Potential GroEL/Hsp60 epitopes on PrP 3479.6 Conformations of chaperonin-bound PrP 3499.7 Conserved Hsp60 substrate binding sites 3499.8 Requirement of ATP-hydrolysis 3519.9 Hsp60-mediated prion propagation 35410. Template-assisted annealing model 35511. Acknowledgments 35712. References 357Although the central paradigm of protein folding (Anfinsen, 1973), that the unique three-dimensional structure of a protein is encoded in its amino acid sequence, is well established, its generality has been questioned due to two recent developments in molecular biology, the ‘prion’ and ‘molecular chaperone’. Biochemical characterization of infectious scrapie material causing central nervous system (CNS) degeneration indicates that the necessary component for disease propagation is proteinaceous (Prusiner, 1982), as first outlined by Griffith (1967) in general terms, and involves a conversion from a cellular prion protein, denoted PrPC, into a toxic scrapie form, PrPSc, which is facilitated by PrPSc acting as a template for PrPC to form new PrPSc molecules (Prusiner, 1987). The ‘protein-only’ hypothesis implies that the same polypeptide sequence, in the absence of any post-translational modifications, can adopt two considerably different stable protein conformations (Fig. 1). Thus, in the case of prions it is possible, although not proven, that they violate the central paradigm of protein folding. There is some indirect evidence that another factor, provisionally named ‘protein X’, might be involved in the conformational conversion process (Prusiner et al. 1998), which includes a dramatic change from α-helical into β-sheet secondary structure (Fig. 1). This factor has not been identified yet, but it has been proposed that protein X may act as a molecular chaperone. The idea that molecular chaperones play a critical role in the generation of PrPSc is appealing also from a theoretical point of view, because PrPSc formation involves changes in protein folding and possibly intermolecular aggregation (Fig. 1), processes in which chaperones are known to participate (Musgrove & Ellis, 1986). The discovery and functional analysis of more than a dozen molecular chaperones made it clear that these proteins do not complement folding information that is not already contained in the genetic code (Ellis et al. 1989); rather they facilitate the folding and assembly of proteins by preventing misfolding and refolding misfolded proteins (Hartl, 1996). Whether a molecular chaperone or another type of macromolecule is identified as the conversion factor, therefore, the molecular chaperone concept is likely to contribute to the understanding of the molecular nature of PrPC to PrPSc conversion.In this review I consider the prion concept from the view of a structural biologist whose main interest focuses on spontaneous and chaperone-mediated conformational changes in proteins.
7
Muronetz, Vladimir I., Sofia S. Kudryavtseva, Evgeniia V. Leisi, Lidia P. Kurochkina, Kseniya V. Barinova, and Elena V. Schmalhausen. "Regulation by Different Types of Chaperones of Amyloid Transformation of Proteins Involved in the Development of Neurodegenerative Diseases." International Journal of Molecular Sciences 23, no. 5 (March 2, 2022): 2747. http://dx.doi.org/10.3390/ijms23052747.
Full textAbstract:
The review highlights various aspects of the influence of chaperones on amyloid proteins associated with the development of neurodegenerative diseases and includes studies conducted in our laboratory. Different sections of the article are devoted to the role of chaperones in the pathological transformation of alpha-synuclein and the prion protein. Information about the interaction of the chaperonins GroE and TRiC as well as polymer-based artificial chaperones with amyloidogenic proteins is summarized. Particular attention is paid to the effect of blocking chaperones by misfolded and amyloidogenic proteins. It was noted that the accumulation of functionally inactive chaperones blocked by misfolded proteins might cause the formation of amyloid aggregates and prevent the disassembly of fibrillar structures. Moreover, the blocking of chaperones by various forms of amyloid proteins might lead to pathological changes in the vital activity of cells due to the impaired folding of newly synthesized proteins and their subsequent processing. The final section of the article discusses both the little data on the role of gut microbiota in the propagation of synucleinopathies and prion diseases and the possible involvement of the bacterial chaperone GroE in these processes.
8
Ellis, R. John. "Assembly chaperones: a perspective." Philosophical Transactions of the Royal Society B: Biological Sciences 368, no. 1617 (May 5, 2013): 20110398. http://dx.doi.org/10.1098/rstb.2011.0398.
Full textAbstract:
The historical origins and current interpretation of the molecular chaperone concept are presented, with the emphasis on the distinction between folding chaperones and assembly chaperones. Definitions of some basic terms in this field are offered and misconceptions pointed out. Two examples of assembly chaperone are discussed in more detail: the role of numerous histone chaperones in fundamental nuclear processes and the co-operation of assembly chaperones with folding chaperones in the production of the world's most important enzyme.
9
Zuehlke, Abbey D., Michael A. Moses, and Len Neckers. "Heat shock protein 90: its inhibition and function." Philosophical Transactions of the Royal Society B: Biological Sciences 373, no. 1738 (December 4, 2017): 20160527. http://dx.doi.org/10.1098/rstb.2016.0527.
Full textAbstract:
The molecular chaperone heat shock protein 90 (Hsp90) facilitates metastable protein maturation, stabilization of aggregation-prone proteins, quality control of misfolded proteins and assists in keeping proteins in activation-competent conformations. Proteins that rely on Hsp90 for function are delivered to Hsp90 utilizing a co-chaperone–assisted cycle. Co-chaperones play a role in client transfer to Hsp90, Hsp90 ATPase regulation and stabilization of various Hsp90 conformational states. Many of the proteins chaperoned by Hsp90 (Hsp90 clients) are essential for the progression of various diseases, including cancer, Alzheimer's disease and other neurodegenerative diseases, as well as viral and bacterial infections. Given the importance of these clients in different diseases and their dynamic interplay with the chaperone machinery, it has been suggested that targeting Hsp90 and its respective co-chaperones may be an effective method for combating a large range of illnesses. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
10
Modgil, V., R. Barratt, DJ Summerton, and A. Muneer. "Chaperone use amongst UK urological surgeons – an evaluation of current practice and opinion." Annals of The Royal College of Surgeons of England 98, no. 04 (April 1, 2016): 268–69. http://dx.doi.org/10.1308/rcsann.2016.0071.
Full textAbstract:
Introduction Intimate examinations are routinely performed by urologists as part of clinical practice. To protect patients and doctors, the General Medical Council offers guidance on the use of chaperones for intimate examinations. We assessed the opinions and use of chaperones amongst members of the British Association of Urological Surgeons (BAUS). Methods An online questionnaire comprising 12 questions on the use of chaperones in clinical practice was sent to all full, trainee and speciality doctor members of BAUS. Results The questionnaire had a response rate of 26% (n=331). The majority of respondents were consultant urologists, comprising 78.8% (n=261), with a wide range of years of experience. Of the respondents, 38.9% were not aware of the GMC guidance on chaperones. While 72.5% always used a chaperone., 22.9% never use a chaperone when the patient was of the same sex. Chaperones were most commonly used for intimate examinations (64.6%), and for examinations involving members of the opposite sex (77.3%). A majority of respondents felt that chaperones protect both the patient (77.3%), and the doctor (96.6%). However, 42.5% did not feel that using a chaperone assists the doctor’s examination, and some (17.2%) participants felt that chaperones were unnecessary. Conclusions This study shows considerable variability amongst urologists in their use of chaperones. A significant proportion of respondents were not aware of the GMC guidelines and did not regularly use a chaperone during an intimate examination. In addition, practice appears to be gender biased. Further study and education is suggested.
11
Altinok, Selin, Rebekah Sanchez-Hodge, Mariah Stewart, Kaitlan Smith, and Jonathan C. Schisler. "With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage." Cells 10, no. 11 (November 11, 2021): 3121. http://dx.doi.org/10.3390/cells10113121.
Full textAbstract:
Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintain protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensure cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, with a concentration on cardioprotection, neuroprotection, cancer, and autoimmune diseases. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones.
12
Griffith, Alijah A., and William Holmes. "Fine Tuning: Effects of Post-Translational Modification on Hsp70 Chaperones." International Journal of Molecular Sciences 20, no. 17 (August 28, 2019): 4207. http://dx.doi.org/10.3390/ijms20174207.
Full textAbstract:
The discovery of heat shock proteins shaped our view of protein folding in the cell. Since their initial discovery, chaperone proteins were identified in all domains of life, demonstrating their vital and conserved functional roles in protein homeostasis. Chaperone proteins maintain proper protein folding in the cell by utilizing a variety of distinct, characteristic mechanisms to prevent aberrant intermolecular interactions, prevent protein aggregation, and lower entropic costs to allow for protein refolding. Continued study has found that chaperones may exhibit alternative functions, including maintaining protein folding during endoplasmic reticulum (ER) import and chaperone-mediated degradation, among others. Alternative chaperone functions are frequently controlled by post-translational modification, in which a given chaperone can switch between functions through covalent modification. This review will focus on the Hsp70 class chaperones and their Hsp40 co-chaperones, specifically highlighting the importance of post-translational control of chaperones. These modifications may serve as a target for therapeutic intervention in the treatment of diseases of protein misfolding and aggregation.
13
Ranford, Julia C., Anthony R. M. Coates, and Brian Henderson. "Chaperonins are cell-signalling proteins: the unfolding biology of molecular chaperones." Expert Reviews in Molecular Medicine 2, no. 8 (September 15, 2000): 1–17. http://dx.doi.org/10.1017/s1462399400002015.
Full textAbstract:
The chaperonins are a subgroup of oligomeric molecular chaperones; the best-studied examples are chaperonin 60 (GroEL) and chaperonin 10 (GroES), both from the bacterium Escherichia coli. At the end of the 20th century, the paradigm of chaperonins as protein folders had emerged, but it is likely that during the 21st century these proteins will come to be viewed as intercellular signals. Indeed, it is possible that the chaperonins were among the first intercellular signalling proteins to evolve. During the past few years, it has emerged that chaperonin 10 and chaperonin 60 can be found on the surface of various prokaryotic and eukaryotic cells, and can even be released from cells. Secreted chaperonins can interact with a variety of cell types, including leukocytes, vascular endothelial cells and epithelial cells, and activate key cellular activities such as the synthesis of cytokines and adhesion proteins. Much has been made of the high degree of sequence conservation among the chaperonins, particularly in terms of the immunogenicity of these proteins. However, different chaperonin 60 proteins can bind to different cell-surface receptors, including the Toll-like receptors, suggesting that this family of proteins cannot be treated as one biological entity and that several subfamilies may exist. Chaperonins have been implicated in human diseases on the basis of their immunogenicity. The finding that chaperonins can also induce tissue pathology suggests that they may play roles in infections and in idiopathic diseases such as atherosclerosis and arthritis.
14
Bohush, Anastasiia, Paweł Bieganowski, and Anna Filipek. "Hsp90 and Its Co-Chaperones in Neurodegenerative Diseases." International Journal of Molecular Sciences 20, no. 20 (October 9, 2019): 4976. http://dx.doi.org/10.3390/ijms20204976.
Full textAbstract:
Proper folding is crucial for proteins to achieve functional activity in the cell. However, it often occurs that proteins are improperly folded (misfolded) and form aggregates, which are the main hallmark of many diseases including cancers, neurodegenerative diseases and many others. Proteins that assist other proteins in proper folding into three-dimensional structures are chaperones and co-chaperones. The key role of chaperones/co-chaperones is to prevent protein aggregation, especially under stress. An imbalance between chaperone/co-chaperone levels has been documented in neurons, and suggested to contribute to protein misfolding. An essential protein and a major regulator of protein folding in all eukaryotic cells is the heat shock protein 90 (Hsp90). The function of Hsp90 is tightly regulated by many factors, including co-chaperones. In this review we summarize results regarding the role of Hsp90 and its co-chaperones in neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and prionopathies.
15
Rief, Matthias, and Gabriel Žoldák. "Single-molecule mechanical studies of chaperones and their clients." Biophysics Reviews 3, no. 4 (December 2022): 041301. http://dx.doi.org/10.1063/5.0098033.
Full textAbstract:
Single-molecule force spectroscopy provides access to the mechanics of biomolecules. Recently, magnetic and laser optical tweezers were applied in the studies of chaperones and their interaction with protein clients. Various aspects of the chaperone–client interactions can be revealed based on the mechanical probing strategies. First, when a chaperone is probed under load, one can examine the inner workings of the chaperone while it interacts with and works on the client protein. Second, when protein clients are probed under load, the action of chaperones on folding clients can be studied in great detail. Such client folding studies have given direct access to observing actions of chaperones in real-time, like foldase, unfoldase, and holdase activity. In this review, we introduce the various single molecule mechanical techniques and summarize recent single molecule mechanical studies on heat shock proteins, chaperone-mediated folding on the ribosome, SNARE folding, and studies of chaperones involved in the folding of membrane proteins. An outlook on significant future developments is given.
16
Alvarez-Ponce, David, José Aguilar-Rodríguez, and Mario A. Fares. "Molecular Chaperones Accelerate the Evolution of Their Protein Clients in Yeast." Genome Biology and Evolution 11, no. 8 (July 11, 2019): 2360–75. http://dx.doi.org/10.1093/gbe/evz147.
Full textAbstract:
Abstract Protein stability is a major constraint on protein evolution. Molecular chaperones, also known as heat-shock proteins, can relax this constraint and promote protein evolution by diminishing the deleterious effect of mutations on protein stability and folding. This effect, however, has only been stablished for a few chaperones. Here, we use a comprehensive chaperone–protein interaction network to study the effect of all yeast chaperones on the evolution of their protein substrates, that is, their clients. In particular, we analyze how yeast chaperones affect the evolutionary rates of their clients at two very different evolutionary time scales. We first study the effect of chaperone-mediated folding on protein evolution over the evolutionary divergence of Saccharomyces cerevisiae and S. paradoxus. We then test whether yeast chaperones have left a similar signature on the patterns of standing genetic variation found in modern wild and domesticated strains of S. cerevisiae. We find that genes encoding chaperone clients have diverged faster than genes encoding non-client proteins when controlling for their number of protein–protein interactions. We also find that genes encoding client proteins have accumulated more intraspecific genetic diversity than those encoding non-client proteins. In a number of multivariate analyses, controlling by other well-known factors that affect protein evolution, we find that chaperone dependence explains the largest fraction of the observed variance in the rate of evolution at both evolutionary time scales. Chaperones affecting rates of protein evolution mostly belong to two major chaperone families: Hsp70s and Hsp90s. Our analyses show that protein chaperones, by virtue of their ability to buffer destabilizing mutations and their role in modulating protein genotype–phenotype maps, have a considerable accelerating effect on protein evolution.
17
Paladino, Letizia, Alessandra Vitale, Radha Santonocito, Alessandro Pitruzzella, Calogero Cipolla, Giuseppa Graceffa, Fabio Bucchieri, Everly Conway de Macario, Alberto Macario, and Francesca Rappa. "Molecular Chaperones and Thyroid Cancer." International Journal of Molecular Sciences 22, no. 8 (April 18, 2021): 4196. http://dx.doi.org/10.3390/ijms22084196.
Full textAbstract:
Thyroid cancers are the most common of the endocrine system malignancies and progress must be made in the areas of differential diagnosis and treatment to improve patient management. Advances in the understanding of carcinogenic mechanisms have occurred in various fronts, including studies of the chaperone system (CS). Components of the CS are found to be quantitatively increased or decreased, and some correlations have been established between the quantitative changes and tumor type, prognosis, and response to treatment. These correlations provide the basis for identifying distinctive patterns useful in differential diagnosis and for planning experiments aiming at elucidating the role of the CS in tumorigenesis. Here, we discuss studies of the CS components in various thyroid cancers (TC). The chaperones belonging to the families of the small heat-shock proteins Hsp70 and Hsp90 and the chaperonin of Group I, Hsp60, have been quantified mostly by immunohistochemistry and Western blot in tumor and normal control tissues and in extracellular vesicles. Distinctive differences were revealed between the various thyroid tumor types. The most frequent finding was an increase in the chaperones, which can be attributed to the augmented need for chaperones the tumor cells have because of their accelerated metabolism, growth, and division rate. Thus, chaperones help the tumor cell rather than protect the patient, exemplifying chaperonopathies by mistake or collaborationism. This highlights the need for research on chaperonotherapy, namely the development of means to eliminate/inhibit pathogenic chaperones.
18
Meimaridou, Eirini, Sakina B. Gooljar, and J. Paul Chapple. "From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery." Journal of Molecular Endocrinology 42, no. 1 (October 13, 2008): 1–9. http://dx.doi.org/10.1677/jme-08-0116.
Full textAbstract:
Molecular chaperones are best recognized for their roles in de novo protein folding and the cellular response to stress. However, many molecular chaperones, and in particular the Hsp70 chaperone machinery, have multiple diverse cellular functions. At the molecular level, chaperones are mediators of protein conformational change. To facilitate conformational change of client/substrate proteins, in manifold contexts, chaperone power must be closely regulated and harnessed to specific cellular locales – this is controlled by cochaperones. This review considers specialized functions of the Hsp70 chaperone machinery mediated by its cochaperones. We focus on vesicular trafficking, protein degradation and a potential role in G protein-coupled receptor processing.
19
Huang, Yan, Yaxin Dai, and Zheng Zhou. "Mechanistic and structural insights into histone H2A–H2B chaperone in chromatin regulation." Biochemical Journal 477, no. 17 (September 17, 2020): 3367–86. http://dx.doi.org/10.1042/bcj20190852.
Full textAbstract:
Histone chaperones include a wide variety of proteins which associate with histones and regulate chromatin structure. The classic H2A–H2B type of histone chaperones, and the chromatin remodeling complex components possessing H2A–H2B chaperone activity, show a broad range of structures and functions. Rapid progress in the structural and functional study of H2A–H2B chaperones extends our knowledge about the epigenetic regulation of chromatin. In this review, we summarize the most recent advances in the understanding of the structure and function of H2A–H2B chaperones that interact with either canonical or variant H2A–H2B dimers. We discuss the current knowledge of the H2A–H2B chaperones, which present no preference for canonical and variant H2A–H2B dimers, describing how they interact with H2A–H2B to fulfill their functions. We also review recent advances of H2A variant-specific chaperones, demarcating how they achieve specific recognition for histone variant H2A.Z and how these interactions regulate chromatin structure by nucleosome editing. We highlight the universal mechanism underlying H2A–H2B dimers recognition by a large variety of histone chaperones. These findings will shed insight into the biological impacts of histone chaperone, chromatin remodeling complex, and histone variants in chromatin regulation.
20
Lund, Peter. "Insights into chaperonin function from studies on archaeal thermosomes." Biochemical Society Transactions 39, no. 1 (January 19, 2011): 94–98. http://dx.doi.org/10.1042/bst0390094.
Full textAbstract:
It is now well understood that, although proteins fold spontaneously (in a thermodynamic sense), many nevertheless require the assistance of helpers called molecular chaperones to reach their correct and active folded state in living cells. This is because the pathways of protein folding are full of traps for the unwary: the forces that drive proteins into their folded states can also drive them into insoluble aggregates, and, particularly when cells are stressed, this can lead, without prevention or correction, to cell death. The chaperonins are a family of molecular chaperones, practically ubiquitous in all living organisms, which possess a remarkable structure and mechanism of action. They act as nanoboxes in which proteins can fold, isolated from their environment and from other partners with which they might, with potentially deleterious consequences, interact. The opening and closing of these boxes is timed by the binding and hydrolysis of ATP. The chaperonins which are found in bacteria are extremely well characterized, and, although those found in archaea (also known as thermosomes) and eukaryotes have received less attention, our understanding of these proteins is constantly improving. This short review will summarize what we know about chaperonin function in the cell from studies on the archaeal chaperonins, and show how recent work is improving our understanding of this essential class of molecular chaperones.
21
Kovacs, Denes, and Peter Tompa. "Diverse functional manifestations of intrinsic structural disorder in molecular chaperones." Biochemical Society Transactions 40, no. 5 (September 19, 2012): 963–68. http://dx.doi.org/10.1042/bst20120108.
Full textAbstract:
IDPs (intrinsically disordered proteins) represent a unique class of proteins which show diverse molecular mechanisms in key biological functions. The aim of the present mini-review is to summarize IDP chaperones that have increasingly been studied in the last few years, by focusing on the role of intrinsic disorder in their molecular mechanism. Disordered regions in both globular and disordered chaperones are often involved directly in chaperone action, either by modulating activity or through direct involvement in substrate identification and binding. They might also be responsible for the subcellular localization of the protein. In outlining the state of the art, we survey known IDP chaperones discussing the following points: (i) globular chaperones that have an experimentally proven functional disordered region(s), (ii) chaperones that are completely disordered along their entire length, and (iii) the possible mechanisms of action of disordered chaperones. Through all of these details, we chart out how far the field has progressed, only to emphasize the long road ahead before the chaperone function can be firmly established as part of the physiological mechanistic arsenal of the emerging group of IDPs.
22
Eggers, D. K., W. J. Welch, and W. J. Hansen. "Complexes between nascent polypeptides and their molecular chaperones in the cytosol of mammalian cells." Molecular Biology of the Cell 8, no. 8 (August 1997): 1559–73. http://dx.doi.org/10.1091/mbc.8.8.1559.
Full textAbstract:
Folding of newly synthesized proteins in vivo is believed to be facilitated by the cooperative interaction of a defined group of proteins known as molecular chaperones. We investigated the direct interaction of chaperones with nascent polypeptides in the cytosol of mammalian cells by multiple methods. A new approach using a polyclonal antibody to puromycin allowed us to tag and capture a population of truncated nascent polypeptides with no bias as to the identity of the bound chaperones. In addition, antibodies that recognize the cytosolic chaperones hsp70, CCT (TRiC), hsp40, p48 (Hip), and hsp90 were compared on the basis of their ability to coprecipitate nascent polypeptides, both before and after chemical cross-linking. By all three approaches, hsp70 was found to be the predominant chaperone bound to nascent polypeptides. The interaction between hsp70 and nascent polypeptides is apparently dynamic under physiological conditions but can be stabilized by depletion of ATP or by cross-linking. The cytosolic chaperonin CCT was found to bind primarily to full-length, newly synthesized actin, and tubulin. We demonstrate and caution that nascent polypeptides have a propensity for binding many proteins nonspecifically in cell lysates. Although current models of protein folding in vivo have described additional components in contact with nascent polypeptides, our data indicate that the hsp70 and, perhaps, the hsp90 families are the predominant classes of molecular chaperones that interact with the general population of cytosolic nascent polypeptides.
23
Backe, Sarah J., Rebecca A. Sager, Katherine A. Meluni, Mark R. Woodford, Dimitra Bourboulia, and Mehdi Mollapour. "Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer." Biomolecules 12, no. 7 (July 1, 2022): 928. http://dx.doi.org/10.3390/biom12070928.
Full textAbstract:
Heat shock protein-90 (Hsp90) is an ATP-dependent molecular chaperone that is tightly regulated by a group of proteins termed co-chaperones. This chaperone system is essential for the stabilization and activation of many key signaling proteins. Recent identification of the co-chaperones FNIP1, FNIP2, and Tsc1 has broadened the spectrum of Hsp90 regulators. These new co-chaperones mediate the stability of critical tumor suppressors FLCN and Tsc2 as well as the various classes of Hsp90 kinase and non-kinase clients. Many early observations of the roles of FNIP1, FNIP2, and Tsc1 suggested functions independent of FLCN and Tsc2 but have not been fully delineated. Given the broad cellular impact of Hsp90-dependent signaling, it is possible to explain the cellular activities of these new co-chaperones by their influence on Hsp90 function. Here, we review the literature on FNIP1, FNIP2, and Tsc1 as co-chaperones and discuss the potential downstream impact of this regulation on normal cellular function and in human diseases.
24
Csermely, Peter. "A Nonconventional Role of Molecular Chaperones: Involvement in the Cytoarchitecture." Physiology 16, no. 3 (June 2001): 123–26. http://dx.doi.org/10.1152/physiologyonline.2001.16.3.123.
Full textAbstract:
A hallmark of chaperone action is assistance in protein folding. Indeed, folding of nascent prokaryotic proteins proceeds mostly as a chaperone-assisted, posttranslational event. On the contrary, in nonstressed eukaryotic cells folding-related tasks of eukaryotic chaperones are restricted to a subset of proteins, and “jobless” chaperones may form an extension of the cytoarchitecture, facilitating intracellular traffic of proteins and other macromolecules.
25
Naylor, Dean J., and F. Ulrich Hartl. "Contribution of molecular chaperones to protein folding in the cytoplasm of prokaryotic and eukaryotic cells." Biochemical Society Symposia 68 (August 1, 2001): 45–68. http://dx.doi.org/10.1042/bss0680045.
Full textAbstract:
While it is clear that many unfolded proteins can attain their native state spontaneously in vitro, the efficiency of such folding is usually limited to conditions far removed from those encountered within cells. Two properties of the cellular environment are expected to enhance strongly the propensity of incompletely folded polypeptides to misfold and aggregate: the crowding effect caused by the high concentration of macromolecules, and the close proximity of nascent polypeptide chains emerging from polyribosomes. However, in the living cell, non-productive protein folding is in many, if not most, cases prevented by the action of a highly conserved set of proteins termed molecular chaperones. In the cytoplasm, the Hsp70 (heat-shock protein of 70 kDa) and chaperonin families of molecular chaperones appear to be the major contributors to efficient protein folding during both normal conditions and adverse conditions such as heat stress. Hsp70 chaperones recognize and shield short, hydrophobic peptide segments in the context of non-native polypeptides and probably promote folding by decreasing the concentration of aggregation-prone intermediates. In contrast, the chaperonins interact with and globally enclose collapsed folding intermediates in a central cavity where efficient folding can proceed in a protected environment. For a number of proteins, folding requires the co-ordinated action of both of these molecular chaperones.
26
Galai, Geut, Hila Ben-David, Liron Levin, Martin F. Orth, Thomas G. P. Grünewald, Shai Pilosof, Shimon Bershtein, and Barak Rotblat. "Pan-Cancer Analysis of Mitochondria Chaperone-Client Co-Expression Reveals Chaperone Functional Partitioning." Cancers 12, no. 4 (March 30, 2020): 825. http://dx.doi.org/10.3390/cancers12040825.
Full textAbstract:
Metabolic reprogramming is a hallmark of cancer. Such reprogramming entails the up-regulation of the expression of specific mitochondrial proteins, thus increasing the burden on the mitochondrial protein quality control. However, very little is known about the specificity of interactions between mitochondrial chaperones and their clients, or to what extent the mitochondrial chaperone–client co-expression is coordinated. We hypothesized that a physical interaction between a chaperone and its client in mitochondria ought to be manifested in the co-expression pattern of both transcripts. Using The Cancer Genome Atlas (TCGA) gene expression data from 13 tumor entities, we constructed the mitochondrial chaperone-client co-expression network. We determined that the network is comprised of three distinct modules, each populated with unique chaperone-clients co-expression pairs belonging to distinct functional groups. Surprisingly, chaperonins HSPD1 and HSPE1, which are known to comprise a functional complex, each occupied a different module: HSPD1 co-expressed with tricarboxylic acid cycle cycle enzymes, while HSPE1 co-expressed with proteins involved in oxidative phosphorylation. Importantly, we found that the genes in each module were enriched for discrete transcription factor binding sites, suggesting the mechanism for the coordinated co-expression. We propose that our mitochondrial chaperone–client interactome can facilitate the identification of chaperones supporting specific mitochondrial pathways and bring forth a fundamental principle in metabolic adaptation.
27
Poulet, Axel, Ellyn Rousselot, Stéphane Téletchéa, Céline Noirot, Yannick Jacob, Josien van Wolfswinkel, Christophe Thiriet, and Céline Duc. "The Histone Chaperone Network Is Highly Conserved in Physarum polycephalum." International Journal of Molecular Sciences 24, no. 2 (January 5, 2023): 1051. http://dx.doi.org/10.3390/ijms24021051.
Full textAbstract:
The nucleosome is composed of histones and DNA. Prior to their deposition on chromatin, histones are shielded by specialized and diverse proteins known as histone chaperones. They escort histones during their entire cellular life and ensure their proper incorporation in chromatin. Physarum polycephalum is a Mycetozoan, a clade located at the crown of the eukaryotic tree. We previously found that histones, which are highly conserved between plants and animals, are also highly conserved in Physarum. However, histone chaperones differ significantly between animal and plant kingdoms, and this thus probed us to further study the conservation of histone chaperones in Physarum and their evolution relative to animal and plants. Most of the known histone chaperones and their functional domains are conserved as well as key residues required for histone and chaperone interactions. Physarum is divergent from yeast, plants and animals, but PpHIRA, PpCABIN1 and PpSPT6 are similar in structure to plant orthologues. PpFACT is closely related to the yeast complex, and the Physarum genome encodes the animal-specific APFL chaperone. Furthermore, we performed RNA sequencing to monitor chaperone expression during the cell cycle and uncovered two distinct patterns during S-phase. In summary, our study demonstrates the conserved role of histone chaperones in handling histones in an early-branching eukaryote.
28
Fink, Anthony L. "Chaperone-Mediated Protein Folding." Physiological Reviews 79, no. 2 (April 1, 1999): 425–49. http://dx.doi.org/10.1152/physrev.1999.79.2.425.
Full textAbstract:
The folding of most newly synthesized proteins in the cell requires the interaction of a variety of protein cofactors known as molecular chaperones. These molecules recognize and bind to nascent polypeptide chains and partially folded intermediates of proteins, preventing their aggregation and misfolding. There are several families of chaperones; those most involved in protein folding are the 40-kDa heat shock protein (HSP40; DnaJ), 60-kDa heat shock protein (HSP60; GroEL), and 70-kDa heat shock protein (HSP70; DnaK) families. The availability of high-resolution structures has facilitated a more detailed understanding of the complex chaperone machinery and mechanisms, including the ATP-dependent reaction cycles of the GroEL and HSP70 chaperones. For both of these chaperones, the binding of ATP triggers a critical conformational change leading to release of the bound substrate protein. Whereas the main role of the HSP70/HSP40 chaperone system is to minimize aggregation of newly synthesized proteins, the HSP60 chaperones also facilitate the actual folding process by providing a secluded environment for individual folding molecules and may also promote the unfolding and refolding of misfolded intermediates.
29
Liu, Wallace H., and Mair E. A. Churchill. "Histone transfer among chaperones." Biochemical Society Transactions 40, no. 2 (March 21, 2012): 357–63. http://dx.doi.org/10.1042/bst20110737.
Full textAbstract:
The eukaryotic processes of nucleosome assembly and disassembly govern chromatin dynamics, in which histones exchange in a highly regulated manner to promote genome accessibility for all DNA-dependent processes. This regulation is partly carried out by histone chaperones, which serve multifaceted roles in co-ordinating the interactions of histone proteins with modification enzymes, nucleosome remodellers, other histone chaperones and nucleosomal DNA. The molecular details of the processes by which histone chaperones promote delivery of histones among their many functional partners are still largely undefined, but promise to offer insights into epigenome maintenance. In the present paper, we review recent findings on the histone chaperone interactions that guide the assembly of histones H3 and H4 into chromatin. This evidence supports the concepts of histone post-translational modifications and specific histone chaperone interactions as guiding principles for histone H3/H4 transactions during chromatin assembly.
30
Borges, Júlio C., Maria C. Peroto, and Carlos H. I. Ramos. "Molecular chaperone genes in the sugarcane expressed sequence database (SUCEST)." Genetics and Molecular Biology 24, no. 1-4 (December 2001): 85–92. http://dx.doi.org/10.1590/s1415-47572001000100013.
Full textAbstract:
Some newly synthesized proteins require the assistance of molecular chaperones for their correct folding. Chaperones are also involved in the dissolution of protein aggregates making their study significant for both biotechnology and medicine and the identification of chaperones and stress-related protein sequences in different organisms is an important task. We used bioinformatic tools to investigate the information generated by the Sugarcane Expressed Sequence Tag (SUCEST) genome project in order to identify and annotate molecular chaperones. We considered that the SUCEST sequences belonged to this category of proteins when their E-values were lower than 1.0e-05. Our annotation shows that 4,164 of the 5’ expressed sequence tag (EST) sequences were homologous to molecular chaperones, nearly 1.8% of all the 5’ ESTs sequenced during the SUCEST project. About 43% of the chaperones which we found were Hsp70 chaperones and its co-chaperones, 10% were Hsp90 chaperones and 13% were peptidyl-prolyl cis, trans isomerase. Based on the annotation results we predicted 156 different chaperone gene subclasses in the sugarcane genome. Taken together, our results indicate that genes which encode chaperones were diverse and abundantly expressed in sugarcane cells, which emphasizes their biological importance.
31
Kinger, Sumit, Ankur Rakesh Dubey, Prashant Kumar, Yuvraj Anandrao Jagtap, Akash Choudhary, Amit Kumar, Vijay Kumar Prajapati, Rohan Dhiman, and Amit Mishra. "Molecular Chaperones’ Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis." Cells 12, no. 9 (May 2, 2023): 1302. http://dx.doi.org/10.3390/cells12091302.
Full textAbstract:
Amyotrophic lateral sclerosis (ALS) is a neuronal degenerative condition identified via a build-up of mutant aberrantly folded proteins. The native folding of polypeptides is mediated by molecular chaperones, preventing their pathogenic aggregation. The mutant protein expression in ALS is linked with the entrapment and depletion of chaperone capacity. The lack of a thorough understanding of chaperones’ involvement in ALS pathogenesis presents a significant challenge in its treatment. Here, we review how the accumulation of the ALS-linked mutant FUS, TDP-43, SOD1, and C9orf72 proteins damage cellular homeostasis mechanisms leading to neuronal loss. Further, we discuss how the HSP70 and DNAJ family co-chaperones can act as potential targets for reducing misfolded protein accumulation in ALS. Moreover, small HSPB1 and HSPB8 chaperones can facilitate neuroprotection and prevent stress-associated misfolded protein apoptosis. Designing therapeutic strategies by pharmacologically enhancing cellular chaperone capacity to reduce mutant protein proteotoxic effects on ALS pathomechanisms can be a considerable advancement. Chaperones, apart from directly interacting with misfolded proteins for protein quality control, can also filter their toxicity by initiating strong stress-response pathways, modulating transcriptional expression profiles, and promoting anti-apoptotic functions. Overall, these properties of chaperones make them an attractive target for gaining fundamental insights into misfolded protein disorders and designing more effective therapies against ALS.
32
Newton, Danielle C., Christopher K. Fairley, Richard Teague, Basil Donovan, Francis J. Bowden, Jade Bilardi, Marian Pitts, and Marcus Y. Chen. "Australian sexual health practitioners' use of chaperones for genital examinations: a survey of attitudes and practice." Sexual Health 4, no. 2 (2007): 95. http://dx.doi.org/10.1071/sh07025.
Full textAbstract:
Objectives: To examine the current practice and attitudes of Australian sexual health practitioners towards the use of chaperones for genital examinations. Methods: In July 2006, an anonymous, self-completed questionnaire was mailed to members of the Australasian Chapter of Sexual Health Medicine. Results: Of the 166 questionnaires sent to practitioners, 110 (66%) were returned completed. Of the 110 respondents, only 9% and 19% reported that their clinic routinely provided chaperones for all male and female genital examinations, respectively. Among practitioners whose services did not offer chaperones routinely, chaperones were offered with a mean frequency of 19% for female examinations and 8% for male examinations (P = 0.01). Compared to female practitioners, significantly more male practitioners thought a chaperone was important for medico-legal purposes when examining females (72% v. 53%, P < 0.05). Compared to male practitioners, significantly more female practitioners thought a chaperone was sometimes important for patient support when examining male patients (52% v. 26%, P < 0.001). Only 39% (n = 18) of male practitioners and 36% (n = 23) of female practitioners felt that resources spent on chaperones were justified by the benefits they provided. Conclusions: Despite only a minority of practitioners offering chaperones to patients or using them during examinations, many feel they are important for medico-legal reasons and as support for the patient. Best practice may be for services to routinely offer a chaperone and record instances where an offer is declined. This provides patients with choice and practitioners with some level of protection.
33
Quinlan, Roy A., and R. John Ellis. "Chaperones: needed for both the good times and the bad times." Philosophical Transactions of the Royal Society B: Biological Sciences 368, no. 1617 (May 5, 2013): 20130091. http://dx.doi.org/10.1098/rstb.2013.0091.
Full textAbstract:
In this issue, we explore the assembly roles of protein chaperones, mainly through the portal of their associated human diseases (e.g. cardiomyopathy, cataract, neurodegeneration, cancer and neuropathy). There is a diversity to chaperone function that goes beyond the current emphasis in the scientific literature on their undoubted roles in protein folding and refolding. The focus on chaperone-mediated protein folding needs to be broadened by the original Laskey discovery that a chaperone assists the assembly of an oligomeric structure, the nucleosome, and the subsequent suggestion by Ellis that other chaperones may function in assembly processes, as well as in folding. There have been a number of recent discoveries that extend this relatively neglected aspect of chaperone biology to include proteostasis, maintenance of the cellular redox potential, genome stability, transcriptional regulation and cytoskeletal dynamics. So central are these processes that we propose that chaperones stand at the crossroads of life and death because they mediate essential functions, not only during the bad times, but also in the good times. We suggest that chaperones facilitate the success of a species, and hence the evolution of individuals within populations, because of their contributions to so many key cellular processes, of which protein folding is only one.
34
Maillard, Julien, Pierre Genevaux, and Christof Holliger. "Redundancy and specificity of multiple trigger factor chaperones in Desulfitobacteria." Microbiology 157, no. 8 (August 1, 2011): 2410–21. http://dx.doi.org/10.1099/mic.0.050880-0.
Full textAbstract:
The ribosome-bound trigger factor (TF) chaperone assists folding of newly synthesized polypeptides and participates in the assembly of macromolecular complexes. In the present study we showed that multiple distinct TF paralogues are present in genomes of Desulfitobacteria, a bacterial genus known for its ability to grow using organohalide respiration. Two full-length TF chaperones and at least one truncated TF (lacking the N-terminal ribosome-binding domain) were identified, the latter being systematically linked to clusters of reductive dehalogenase genes encoding the key enzymes in organohalide respiration. Using a well-characterized heterologous chaperone-deficient Escherichia coli strain lacking both TF and DnaK chaperones, we demonstrated that all three TF chaperones were functional in vivo, as judged by their ability to partially suppress bacterial growth defects and protein aggregation in the absence of both major E. coli chaperones. Next, we found that the N-terminal truncated TF-like protein PceT functions as a dedicated chaperone for the cognate reductive dehalogenase PceA by solubilizing and stabilizing it in the heterologous system. Finally, we showed that PceT specifically interacts with the twin-arginine signal peptide of PceA. Taken together, our data define PceT (and more generally the new RdhT family) as a class of TF-like chaperones involved in the maturation of proteins secreted by the twin-arginine translocation pathway.
35
Killian, Andrea N., Sarah C. Miller, and Justin K. Hines. "Impact of Amyloid Polymorphism on Prion-Chaperone Interactions in Yeast." Viruses 11, no. 4 (April 16, 2019): 349. http://dx.doi.org/10.3390/v11040349.
Full textAbstract:
Yeast prions are protein-based genetic elements found in the baker’s yeast Saccharomyces cerevisiae, most of which are amyloid aggregates that propagate by fragmentation and spreading of small, self-templating pieces called propagons. Fragmentation is carried out by molecular chaperones, specifically Hsp104, Hsp70, and Hsp40. Like other amyloid-forming proteins, amyloid-based yeast prions exhibit structural polymorphisms, termed “strains” in mammalian systems and “variants” in yeast, which demonstrate diverse phenotypes and chaperone requirements for propagation. Here, the known differential interactions between chaperone proteins and yeast prion variants are reviewed, specifically those of the yeast prions [PSI+], [RNQ+]/[PIN+], and [URE3]. For these prions, differences in variant-chaperone interactions (where known) with Hsp104, Hsp70s, Hsp40s, Sse1, and Hsp90 are summarized, as well as some interactions with chaperones of other species expressed in yeast. As amyloid structural differences greatly impact chaperone interactions, understanding and accounting for these variations may be crucial to the study of chaperones and both prion and non-prion amyloids.
36
Karunanayake, Chamithi, and Richard C. Page. "Cytosolic protein quality control machinery: Interactions of Hsp70 with a network of co-chaperones and substrates." Experimental Biology and Medicine 246, no. 12 (March 17, 2021): 1419–34. http://dx.doi.org/10.1177/1535370221999812.
Full textAbstract:
The chaperone heat shock protein 70 (Hsp70) and its network of co-chaperones serve as a central hub of cellular protein quality control mechanisms. Domain organization in Hsp70 dictates ATPase activity, ATP dependent allosteric regulation, client/substrate binding and release, and interactions with co-chaperones. The protein quality control activities of Hsp70 are classified as foldase, holdase, and disaggregase activities. Co-chaperones directly assisting protein refolding included J domain proteins and nucleotide exchange factors. However, co-chaperones can also be grouped and explored based on which domain of Hsp70 they interact. Here we discuss how the network of cytosolic co-chaperones for Hsp70 contributes to the functions of Hsp70 while closely looking at their structural features. Comparison of domain organization and the structures of co-chaperones enables greater understanding of the interactions, mechanisms of action, and roles played in protein quality control.
37
Scheidt, Tom, Jacqueline A. Carozza, Carl C. Kolbe, Francesco A. Aprile, Olga Tkachenko, Mathias M. J. Bellaiche, Georg Meisl, et al. "The binding of the small heat-shock protein αB-crystallin to fibrils of α-synuclein is driven by entropic forces." Proceedings of the National Academy of Sciences 118, no. 38 (September 13, 2021): e2108790118. http://dx.doi.org/10.1073/pnas.2108790118.
Full textAbstract:
Molecular chaperones are key components of the cellular proteostasis network whose role includes the suppression of the formation and proliferation of pathogenic aggregates associated with neurodegenerative diseases. The molecular principles that allow chaperones to recognize misfolded and aggregated proteins remain, however, incompletely understood. To address this challenge, here we probe the thermodynamics and kinetics of the interactions between chaperones and protein aggregates under native solution conditions using a microfluidic platform. We focus on the binding between amyloid fibrils of α-synuclein, associated with Parkinson’s disease, to the small heat-shock protein αB-crystallin, a chaperone widely involved in the cellular stress response. We find that αB-crystallin binds to α-synuclein fibrils with high nanomolar affinity and that the binding is driven by entropy rather than enthalpy. Measurements of the change in heat capacity indicate significant entropic gain originates from the disassembly of the oligomeric chaperones that function as an entropic buffer system. These results shed light on the functional roles of chaperone oligomerization and show that chaperones are stored as inactive complexes which are capable of releasing active subunits to target aberrant misfolded species.
38
Jeng, Wilson, Sukyeong Lee, Nuri Sung, Jungsoon Lee, and Francis T. F. Tsai. "Molecular chaperones: guardians of the proteome in normal and disease states." F1000Research 4 (December 15, 2015): 1448. http://dx.doi.org/10.12688/f1000research.7214.1.
Full textAbstract:
Proteins must adopt a defined three-dimensional structure in order to gain functional activity, or must they? An ever-increasing number of intrinsically disordered proteins and amyloid-forming polypeptides challenge this dogma. While molecular chaperones and proteases are traditionally associated with protein quality control inside the cell, it is now apparent that molecular chaperones not only promote protein folding in the “forward” direction by facilitating folding and preventing misfolding and aggregation, but also facilitate protein unfolding and even disaggregation resulting in the recovery of functional protein from aggregates. Here, we review our current understanding of ATP-dependent molecular chaperones that harness the energy of ATP binding and hydrolysis to fuel their chaperone functions. An emerging theme is that most of these chaperones do not work alone, but instead function together with other chaperone systems to maintain the proteome. Hence, molecular chaperones are the major component of the proteostasis network that guards and protects the proteome from damage. Furthermore, while a decline of this network is detrimental to cell and organismal health, a controlled perturbation of the proteostasis network may offer new therapeutic avenues against human diseases.
39
Tompa, Peter, and Denes Kovacs. "Intrinsically disordered chaperones in plants and animalsThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process." Biochemistry and Cell Biology 88, no. 2 (April 2010): 167–74. http://dx.doi.org/10.1139/o09-163.
Full textAbstract:
Intrinsically disordered proteins (IDPs) are widespread in eukaryotes and fulfill important functions associated with signaling and regulation. Recent evidence points to a special and thus largely disrespected functional capacity of IDPs—that they can assist the folding of other proteins and prevent their aggregation, i.e., that they can act as chaperones. In this paper, we survey current information available on this phenomenon, with particular focus on (i) the structure and function of IDPs in general, (ii) disordered chaperones in plants, (iii) disordered chaperones in other organisms spanning from insects to mammals, (iv) the possible mechanisms of action of disordered chaperones, and (v) the possibility of two-faced (Janus) chaperone activity of disordered chaperones, which can assist the folding of both RNA and protein substrates. The evidence is most conclusive in the case of plant stress proteins, such as late embryogenesis abundant (LEA) proteins or dehydrins. We will show that the cellular function of LEA proteins in mitigating the damage caused by stress is clear; nevertheless, experiments carried out in vivo must be extended and the molecular mechanism of the action of IDP chaperones also requires clarification. Using these details, we chart out how far the field has progressed only to emphasize the long road ahead before chaperone function can be firmly established as part of the physiological mechanistic arsenal of the emerging group of IDPs.
40
Sokolova, Olga S., Evgeny B. Pichkur, Ekaterina S. Maslova, Lidia P. Kurochkina, Pavel I. Semenyuk, Petr V. Konarev, Valeriya R. Samygina, and Tatiana B. Stanishneva-Konovalova. "Local Flexibility of a New Single-Ring Chaperonin Encoded by Bacteriophage AR9 Bacillus subtilis." Biomedicines 10, no. 10 (September 21, 2022): 2347. http://dx.doi.org/10.3390/biomedicines10102347.
Full textAbstract:
Chaperonins, a family of molecular chaperones, assist protein folding in all domains of life. They are classified into two groups: bacterial variants and those present in endosymbiotic organelles of eukaryotes belong to group I, while group II includes chaperonins from the cytosol of archaea and eukaryotes. Recently, chaperonins of a prospective new group were discovered in giant bacteriophages; however, structures have been determined for only two of them. Here, using cryo-EM, we resolved a structure of a new chaperonin encoded by gene 228 of phage AR9 B. subtilis. This structure has similarities and differences with members of both groups, as well as with other known phage chaperonins, which further proves their diversity.
41
Friesen, Erik L., Mitch L. De Snoo, Luckshi Rajendran, Lorraine V. Kalia, and Suneil K. Kalia. "Chaperone-Based Therapies for Disease Modification in Parkinson’s Disease." Parkinson's Disease 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/5015307.
Full textAbstract:
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by the presence of pathological intracellular aggregates primarily composed of misfolded α-synuclein. This pathology implicates the molecular machinery responsible for maintaining protein homeostasis (proteostasis), including molecular chaperones, in the pathobiology of the disease. There is mounting evidence from preclinical and clinical studies that various molecular chaperones are downregulated, sequestered, depleted, or dysfunctional in PD. Current therapeutic interventions for PD are inadequate as they fail to modify disease progression by ameliorating the underlying pathology. Modulating the activity of molecular chaperones, cochaperones, and their associated pathways offers a new approach for disease modifying intervention. This review will summarize the potential of chaperone-based therapies that aim to enhance the neuroprotective activity of molecular chaperones or utilize small molecule chaperones to promote proteostasis.
42
Kettern, Nadja, Michael Dreiseidler, Riga Tawo, and Jörg Höhfeld. "Chaperone-assisted degradation: multiple paths to destruction." Biological Chemistry 391, no. 5 (May 1, 2010): 481–89. http://dx.doi.org/10.1515/bc.2010.058.
Full textAbstract:
Abstract Molecular chaperones are well known as facilitators of protein folding and assembly. However, in recent years multiple chaperone-assisted degradation pathways have also emerged, including CAP (chaperone-assisted proteasomal degradation), CASA (chaperone-assisted selective autophagy), and CMA (chaperone-mediated autophagy). Within these pathways chaperones facilitate the sorting of non-native proteins to the proteasome and the lysosomal compartment for disposal. Impairment of these pathways contributes to the development of cancer, myopathies, and neurodegenerative diseases. Chaperone-assisted degradation thus represents an essential aspect of cellular proteostasis, and its pharmacological modulation holds the promise to ameliorate some of the most devastating diseases of our time. Here, we discuss recent insights into molecular mechanisms underlying chaperone-assisted degradation in mammalian cells and highlight its biomedical relevance.
43
Stemp, Markus J., Suranjana Guha, F. Ulrich Hartl, and José M. Barral. "Efficient production of native actin upon translation in a bacterial lysate supplemented with the eukaryotic chaperonin TRiC." Biological Chemistry 386, no. 8 (August 1, 2005): 753–57. http://dx.doi.org/10.1515/bc.2005.088.
Full textAbstract:
Abstract Recombinant expression of actin in bacteria results in non-native species that aggregate into inclusion bodies. Actin is a folding substrate of TRiC, the chaperonin of the eukaryotic cytosol. By employing bacterial in vitro translation lysates supplemented with purified chaperones, we have found that TRiC is the only eukaryotic chaperone necessary for correct folding of newly translated actin. The actin thus produced binds deoxyribonuclease I and polymerizes into filaments, hallmarks of its native state. In contrast to its rapid folding in the eukaryotic cytosol, actin translated in TRiC-supplemented bacterial lysate folds with slower kinetics, resembling the kinetics upon refolding from denaturant. Lysate supplementation with the bacterial chaperonin GroEL/ES or the DnaK/DnaJ/GrpE chaperones leads to prevention of actin aggregation, yet fails to support its correct folding. This combination of in vitro bacterial translation and TRiC-assisted folding allows a detailed analysis of the mechanisms necessary for efficient actin folding in vivo. In addition, it provides a robust alternative for the production of substantial amounts of eukaryotic proteins that otherwise misfold or lead to cellular toxicity upon expression in heterologous hosts.
44
Liang, Fu-Cheng, Gerard Kroon, Camille Z. McAvoy, Chris Chi, Peter E. Wright, and Shu-ou Shan. "Conformational dynamics of a membrane protein chaperone enables spatially regulated substrate capture and release." Proceedings of the National Academy of Sciences 113, no. 12 (March 7, 2016): E1615—E1624. http://dx.doi.org/10.1073/pnas.1524777113.
Full textAbstract:
Membrane protein biogenesis poses enormous challenges to cellular protein homeostasis and requires effective molecular chaperones. Compared with chaperones that promote soluble protein folding, membrane protein chaperones require tight spatiotemporal coordination of their substrate binding and release cycles. Here we define the chaperone cycle for cpSRP43, which protects the largest family of membrane proteins, the light harvesting chlorophyll a/b-binding proteins (LHCPs), during their delivery. Biochemical and NMR analyses demonstrate that cpSRP43 samples three distinct conformations. The stromal factor cpSRP54 drives cpSRP43 to the active state, allowing it to tightly bind substrate in the aqueous compartment. Bidentate interactions with the Alb3 translocase drive cpSRP43 to a partially inactive state, triggering selective release of LHCP’s transmembrane domains in a productive unloading complex at the membrane. Our work demonstrates how the intrinsic conformational dynamics of a chaperone enables spatially coordinated substrate capture and release, which may be general to other ATP-independent chaperone systems.
45
Suryawanshi, Yogesh, Surekha Gupta, Hiral Mange, and Manisha Tripathi. "Efficient Production of Yeast Cu-Zn Superoxide Dismutase in the Periplasm of Escherichia coli by Co-expression of Skp Molecular Chaperone." International Journal of Pharmaceutical Sciences and Drug Research 13, no. 03 (March 30, 2020): 311–17. http://dx.doi.org/10.25004/ijpsdr.2021.130311.
Full textAbstract:
Co-expression is a simultaneous expression of two or more proteins. Molecular chaperones are proteins that are naturally produced in the cell and have an essential role in restraining the aggregation of nonnative protein production. Co-expression of target protein alongside molecular chaperones is an efficient way to overcome the problems faced during the expression of recombinant proteins. The present study aims to a co-express protein highly useful in cosmetics, superoxide dismutase (SOD), in the periplasm of E. coli with molecular chaperone Skp. Superoxide dismutase and Skp were placed under the control of the different promoter and terminator systems to maintain separate expression levels. The co-expression of Skp chaperone on cell growth, SOD protein yield, and SOD enzyme activity were evaluated. Skp co-expression was found effective in all three aspects. The yield of Cu-Zn Superoxide dismutase increased from 30.92mg/L to 52.01mg/L when Skp chaperon is co-expressed. No detectable free SOD subunits were observed on western blot, which shows the method of Skp co-expression could be applied to tackle the problem of unprocessed, free protein subunits while expressing the recombinant protein in E. coli periplasm.
46
Santra, Mantu, Daniel W. Farrell, and Ken A. Dill. "Bacterial proteostasis balances energy and chaperone utilization efficiently." Proceedings of the National Academy of Sciences 114, no. 13 (March 14, 2017): E2654—E2661. http://dx.doi.org/10.1073/pnas.1620646114.
Full textAbstract:
Chaperones are protein complexes that help to fold and disaggregate a cell’s proteins. It is not understood how four major chaperone systems of Escherichia coli work together in proteostasis: the recognition, sorting, folding, and disaggregating of the cell’s many different proteins. Here, we model this machine. We combine extensive data on chaperoning, folding, and aggregation rates with expression levels of proteins and chaperones measured at different growth rates. We find that the proteostasis machine recognizes and sorts a client protein based on two biophysical properties of the client’s misfolded state (M state): its stability and its kinetic accessibility from its unfolded state (U state). The machine is energy-efficient (the sickest proteins use the most ATP-expensive chaperones), comprehensive (it can handle any type of protein), and economical (the chaperone concentrations are just high enough to keep the whole proteome folded and disaggregated but no higher). The cell needs higher chaperone levels in two situations: fast growth (when protein production rates are high) and very slow growth (to mitigate the effects of protein degradation). This type of model complements experimental knowledge by showing how the various chaperones work together to achieve the broad folding and disaggregation needs of the cell.
47
Xu, Huafeng. "Non-Equilibrium Protein Folding and Activation by ATP-Driven Chaperones." Biomolecules 12, no. 6 (June 15, 2022): 832. http://dx.doi.org/10.3390/biom12060832.
Full textAbstract:
Recent experimental studies suggest that ATP-driven molecular chaperones can stabilize protein substrates in their native structures out of thermal equilibrium. The mechanism of such non-equilibrium protein folding is an open question. Based on available structural and biochemical evidence, I propose here a unifying principle that underlies the conversion of chemical energy from ATP hydrolysis to the conformational free energy associated with protein folding and activation. I demonstrate that non-equilibrium folding requires the chaperones to break at least one of four symmetry conditions. The Hsp70 and Hsp90 chaperones each break a different subset of these symmetries and thus they use different mechanisms for non-equilibrium protein folding. I derive an upper bound on the non-equilibrium elevation of the native concentration, which implies that non-equilibrium folding only occurs in slow-folding proteins that adopt an unstable intermediate conformation in binding to ATP-driven chaperones. Contrary to the long-held view of Anfinsen’s hypothesis that proteins fold to their conformational free energy minima, my results predict that some proteins may fold into thermodynamically unstable native structures with the assistance of ATP-driven chaperones, and that the native structures of some chaperone-dependent proteins may be shaped by their chaperone-mediated folding pathways.
48
Thomson, Nicholas M., Azusa Saika, Kazunori Ushimaru, Smith Sangiambut, Takeharu Tsuge, David K. Summers, and Easan Sivaniah. "Efficient Production of Active Polyhydroxyalkanoate Synthase in Escherichia coli by Coexpression of Molecular Chaperones." Applied and Environmental Microbiology 79, no. 6 (January 18, 2013): 1948–55. http://dx.doi.org/10.1128/aem.02881-12.
Full textAbstract:
ABSTRACTThe type I polyhydroxyalkanoate synthase fromCupriavidus necatorwas heterologously expressed inEscherichia coliwith simultaneous overexpression of chaperone proteins. Compared to expression of synthase alone (14.55 mg liter−1), coexpression with chaperones resulted in the production of larger total quantities of enzyme, including a larger proportion in the soluble fraction. The largest increase was seen when the GroEL/GroES system was coexpressed, resulting in approximately 6-fold-greater enzyme yields (82.37 mg liter−1) than in the absence of coexpressed chaperones. The specific activity of the purified enzyme was unaffected by coexpression with chaperones. Therefore, the increase in yield was attributed to an enhanced soluble fraction of synthase. Chaperones were also coexpressed with a polyhydroxyalkanoate production operon, resulting in the production of polymers with generally reduced molecular weights. This suggests a potential use for chaperones to control the physical properties of the polymer.
49
Dimant, Hemi, Darius Ebrahimi-Fakhari, and Pamela J. McLean. "Molecular Chaperones and Co-Chaperones in Parkinson Disease." Neuroscientist 18, no. 6 (July 24, 2012): 589–601. http://dx.doi.org/10.1177/1073858412441372.
Full textAbstract:
Parkinson disease, a progressive neurodegenerative disorder, is caused by the pathological accumulation of proteins, including the ubiquitous presynaptic protein α-synuclein. Alterations in the metabolism of α-synuclein have clearly been linked to neurodegeneration, and early steps in the pathological sequence of this protein include the formation of oligomers, fibrils, and small aggregates. Targeting these early steps of oligomerization is one of the main therapeutic approaches in the quest to develop disease-modifying agents. Molecular chaperones, molecules that can mediate the proper folding and refolding of client proteins, are vital to cell function and survival and thus have been explored as potential therapeutic agents. Important to Parkinson disease, chaperones are capable of preventing α-synuclein misfolding, oligomerization, and aggregate formation as shown in vitro and in Parkinson disease animal models. Furthermore, chaperones and associated co-chaperones are closely linked to pathways of protein degradation, like the ubiquitin-proteasome system and autophagy, and are thus able to remove irreversibly misfolded proteins. In this review, we summarize the role of molecular chaperones in Parkinson disease models and discuss the importance of preserving protein homeostasis to prevent neurodegeneration. We also review the growing number of exciting studies that have targeted molecular chaperone function as a novel therapeutic approach.
50
Weeks, Spencer A., William P. Shield, Chandan Sahi, Elizabeth A. Craig, Sabine Rospert, and David J. Miller. "A Targeted Analysis of Cellular Chaperones Reveals Contrasting Roles for Heat Shock Protein 70 in Flock House Virus RNA Replication." Journal of Virology 84, no. 1 (October 14, 2009): 330–39. http://dx.doi.org/10.1128/jvi.01808-09.
Full textAbstract:
ABSTRACT Cytosolic chaperones are a diverse group of ubiquitous proteins that play central roles in multiple processes within the cell, including protein translation, folding, intracellular trafficking, and quality control. These cellular proteins have also been implicated in the replication of numerous viruses, although the full extent of their involvement in viral replication is unknown. We have previously shown that the heat shock protein 40 (hsp40) chaperone encoded by the yeast YDJ1 gene facilitates RNA replication of flock house virus (FHV), a well-studied and versatile positive-sense RNA model virus. To further explore the roles of chaperones in FHV replication, we examined a panel of 30 yeast strains with single deletions of cytosolic proteins that have known or hypothesized chaperone activity. We found that the majority of cytosolic chaperone deletions had no impact on FHV RNA accumulation, with the notable exception of J-domain-containing hsp40 chaperones, where deletion of APJ1 reduced FHV RNA accumulation by 60%, while deletion of ZUO1, JJJ1, or JJJ2 markedly increased FHV RNA accumulation, by 4- to 40-fold. Further studies using cross complementation and double-deletion strains revealed that the contrasting effects of J domain proteins were reproduced by altering expression of the major cytosolic hsp70s encoded by the SSA and SSB families and were mediated in part by divergent effects on FHV RNA polymerase synthesis. These results identify hsp70 chaperones as critical regulators of FHV RNA replication and indicate that cellular chaperones can have both positive and negative regulatory effects on virus replication.