Journal articles: 'Β-amyloid structures'

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Taguchi, Yuzuru, Hiroki Otaki, and Noriyuki Nishida. "Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion Strains." Viruses 11, no. 2 (January 28, 2019): 110. http://dx.doi.org/10.3390/v11020110.

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The mechanism of prion strain diversity remains unsolved. Investigation of inheritance and diversification of protein-based pathogenic information demands the identification of the detailed structures of abnormal isoforms of the prion protein (PrPSc); however, achieving purification is difficult without affecting infectivity. Similar prion-like properties are recognized also in other disease-associated in-register parallel β-sheet amyloids including Tau and α-synuclein (αSyn) amyloids. Investigations into structures of those amyloids via solid-state nuclear magnetic resonance spectroscopy and cryo-electron microscopy recently made remarkable advances due to their relatively small sizes and lack of post-translational modifications. Herein, we review advances regarding pathogenic amyloids, particularly Tau and αSyn, and discuss implications about strain diversity mechanisms of prion/PrPSc from the perspective that PrPSc is an in-register parallel β-sheet amyloid. Additionally, we present our recent data of molecular dynamics simulations of αSyn amyloid, which suggest significance of compatibility between β-sheet propensities of the substrate and local structures of the template for stability of amyloid structures. Detailed structures of αSyn and Tau amyloids are excellent models of pathogenic amyloids, including PrPSc, to elucidate strain diversity and pathogenic mechanisms.

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Chatani, Eri, Keisuke Yuzu, Yumiko Ohhashi, and Yuji Goto. "Current Understanding of the Structure, Stability and Dynamic Properties of Amyloid Fibrils." International Journal of Molecular Sciences 22, no. 9 (April 21, 2021): 4349. http://dx.doi.org/10.3390/ijms22094349.

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Amyloid fibrils are supramolecular protein assemblies represented by a cross-β structure and fibrous morphology, whose structural architecture has been previously investigated. While amyloid fibrils are basically a main-chain-dominated structure consisting of a backbone of hydrogen bonds, side-chain interactions also play an important role in determining their detailed structures and physicochemical properties. In amyloid fibrils comprising short peptide segments, a steric zipper where a pair of β-sheets with side chains interdigitate tightly is found as a fundamental motif. In amyloid fibrils comprising longer polypeptides, each polypeptide chain folds into a planar structure composed of several β-strands linked by turns or loops, and the steric zippers are formed locally to stabilize the structure. Multiple segments capable of forming steric zippers are contained within a single protein molecule in many cases, and polymorphism appears as a result of the diverse regions and counterparts of the steric zippers. Furthermore, the β-solenoid structure, where the polypeptide chain folds in a solenoid shape with side chains packed inside, is recognized as another important amyloid motif. While side-chain interactions are primarily achieved by non-polar residues in disease-related amyloid fibrils, the participation of hydrophilic and charged residues is prominent in functional amyloids, which often leads to spatiotemporally controlled fibrillation, high reversibility, and the formation of labile amyloids with kinked backbone topology. Achieving precise control of the side-chain interactions within amyloid structures will open up a new horizon for designing useful amyloid-based nanomaterials.

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Paulus, Agnes, Anders Engdahl, Yiyi Yang, Antonio Boza-Serrano, Sara Bachiller, Laura Torres-Garcia, Alexander Svanbergsson, et al. "Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease." International Journal of Molecular Sciences 22, no. 7 (March 26, 2021): 3430. http://dx.doi.org/10.3390/ijms22073430.

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Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging nature of characterizing the secondary structure of amyloids in cells. To overcome this and investigate the molecular changes in proteins directly in cells, we used synchrotron-based infrared microspectroscopy, a label-free and non-destructive technique available for in situ molecular imaging, to detect structural changes in proteins and lipids. Specifically, we evaluated the formation of β-sheet structures in different monogenic and bigenic cellular models of Alzheimer’s disease that we generated for this study. We report on the possibility to discern different amyloid signatures directly in cells using infrared microspectroscopy and demonstrate that bigenic (amyloid-β, α-synuclein) and (amyloid-β, Tau) neuron-like cells display changes in β-sheet load. Altogether, our findings support the notion that different molecular mechanisms of amyloid aggregation, as opposed to a common mechanism, are triggered by the specific cellular environment and, therefore, that various mechanisms lead to the development of Alzheimer’s disease.

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Sulatskaya, Anna I., Anastasiia O. Kosolapova, Alexander G. Bobylev, Mikhail V. Belousov, Kirill S. Antonets, Maksim I. Sulatsky, Irina M. Kuznetsova, Konstantin K. Turoverov, Olesya V. Stepanenko, and Anton A. Nizhnikov. "β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis." International Journal of Molecular Sciences 22, no. 21 (October 20, 2021): 11316. http://dx.doi.org/10.3390/ijms222111316.

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Insoluble protein aggregates with fibrillar morphology called amyloids and β-barrel proteins both share a β-sheet-rich structure. Correctly folded β-barrel proteins can not only function in monomeric (dimeric) form, but also tend to interact with one another—followed, in several cases, by formation of higher order oligomers or even aggregates. In recent years, findings proving that β-barrel proteins can adopt cross-β amyloid folds have emerged. Different β-barrel proteins were shown to form amyloid fibrils in vitro. The formation of functional amyloids in vivo by β-barrel proteins for which the amyloid state is native was also discovered. In particular, several prokaryotic and eukaryotic proteins with β-barrel domains were demonstrated to form amyloids in vivo, where they participate in interspecies interactions and nutrient storage, respectively. According to recent observations, despite the variety of primary structures of amyloid-forming proteins, most of them can adopt a conformational state with the β-barrel topology. This state can be intermediate on the pathway of fibrillogenesis (“on-pathway state”), or can be formed as a result of an alternative assembly of partially unfolded monomers (“off-pathway state”). The β-barrel oligomers formed by amyloid proteins possess toxicity, and are likely to be involved in the development of amyloidoses, thus representing promising targets for potential therapy of these incurable diseases. Considering rapidly growing discoveries of the amyloid-forming β-barrels, we may suggest that their real number and diversity of functions are significantly higher than identified to date, and represent only “the tip of the iceberg”. Here, we summarize the data on the amyloid-forming β-barrel proteins, their physicochemical properties, and their biological functions, and discuss probable means and consequences of the amyloidogenesis of these proteins, along with structural relationships between these two widespread types of β-folds.

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Alperstein, Ariel M., Joshua S. Ostrander, Tianqi O. Zhang, and Martin T. Zanni. "Amyloid found in human cataracts with two-dimensional infrared spectroscopy." Proceedings of the National Academy of Sciences 116, no. 14 (March 20, 2019): 6602–7. http://dx.doi.org/10.1073/pnas.1821534116.

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UV light and other factors damage crystallin proteins in the eye lens, resulting in cataracts that scatter light and affect vision. Little information exists about protein structures within these disease-causing aggregates. We examined postmortem lens tissue from individuals with and without cataracts using 2D infrared (2DIR) spectroscopy. Amyloid β-sheet secondary structure was detected in cataract lenses along with denatured structures. No amyloid structures were found in lenses from juveniles, but mature lenses with no cataract diagnosis also contained amyloid, indicating that amyloid structures begin forming before diagnosis. Light scatters more strongly in regions with amyloid structure, and UV light induces amyloid β-sheet structures, linking the presence of amyloid structures to disease pathology. Establishing that age-related cataracts involve amyloid structures gives molecular insight into a common human affliction and provides a possible structural target for pharmaceuticals as an alternative to surgery.

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Freitas, Raul O., Adrian Cernescu, Anders Engdahl, Agnes Paulus, João E. Levandoski, Isak Martinsson, Elke Hebisch, et al. "Nano-Infrared Imaging of Primary Neurons." Cells 10, no. 10 (September 27, 2021): 2559. http://dx.doi.org/10.3390/cells10102559.

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Alzheimer’s disease (AD) accounts for about 70% of neurodegenerative diseases and is a cause of cognitive decline and death for one-third of seniors. AD is currently underdiagnosed, and it cannot be effectively prevented. Aggregation of amyloid-β (Aβ) proteins has been linked to the development of AD, and it has been established that, under pathological conditions, Aβ proteins undergo structural changes to form β-sheet structures that are considered neurotoxic. Numerous intensive in vitro studies have provided detailed information about amyloid polymorphs; however, little is known on how amyloid β-sheet-enriched aggregates can cause neurotoxicity in relevant settings. We used scattering-type scanning near-field optical microscopy (s-SNOM) to study amyloid structures at the nanoscale, in individual neurons. Specifically, we show that in well-validated systems, s-SNOM can detect amyloid β-sheet structures with nanometer spatial resolution in individual neurons. This is a proof-of-concept study to demonstrate that s-SNOM can be used to detect Aβ-sheet structures on cell surfaces at the nanoscale. Furthermore, this study is intended to raise neurobiologists’ awareness of the potential of s-SNOM as a tool for analyzing amyloid β-sheet structures at the nanoscale in neurons without the need for immunolabeling.

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Yu, Xiang, and Jie Zheng. "Polymorphic Structures of Alzheimer's β-Amyloid Globulomers." PLoS ONE 6, no. 6 (June 7, 2011): e20575. http://dx.doi.org/10.1371/journal.pone.0020575.

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8

Yakupova, Elmira I., Liya G. Bobyleva, Sergey A. Shumeyko, Ivan M. Vikhlyantsev, and Alexander G. Bobylev. "Amyloids: The History of Toxicity and Functionality." Biology 10, no. 5 (May 1, 2021): 394. http://dx.doi.org/10.3390/biology10050394.

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Proteins can perform their specific function due to their molecular structure. Partial or complete unfolding of the polypeptide chain may lead to the misfolding and aggregation of proteins in turn, resulting in the formation of different structures such as amyloid aggregates. Amyloids are rigid protein aggregates with the cross-β structure, resistant to most solvents and proteases. Because of their resistance to proteolysis, amyloid aggregates formed in the organism accumulate in tissues, promoting the development of various diseases called amyloidosis, for instance Alzheimer’s diseases (AD). According to the main hypothesis, it is considered that the cause of AD is the formation and accumulation of amyloid plaques of Aβ. That is why Aβ-amyloid is the most studied representative of amyloids. Therefore, in this review, special attention is paid to the history of Aβ-amyloid toxicity. We note the main problems with anti-amyloid therapy and write about new views on amyloids that can play positive roles in the different organisms including humans.

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9

Tycko, Robert. "Molecular structure of amyloid fibrils: insights from solid-state NMR." Quarterly Reviews of Biophysics 39, no. 1 (February 2006): 1–55. http://dx.doi.org/10.1017/s0033583506004173.

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1. Introduction 22. Sources of structural information in solid-state NMR data 52.1 General remarks 52.2 Chemical shifts, linewidths, and magic-angle spinning 62.3 Dipole–dipole couplings and dipolar recoupling 82.4 Tensor correlation techniques 122.5 Solid-state NMR of aligned samples 142.6 Indirect sources of structural information 152.7 Sample preparation for solid-state NMR 153. Levels of structure in amyloid fibrils 184. Molecular structure of β-amyloid fibrils 254.1 Self-propagating, molecular-level polymorphism in Aβ1–40 fibrils 254.2 Structural model for Aβ1-40 fibrils 284.3 Staggering of β-strands in Aβ1-40 fibrils 324.4 Structure of Aβ1-42 fibrils 344.5 Structure of fibrils formed by short β-amyloid fragments 344.6 Structures of non-fibrillar aggregates 355. Molecular structure of other amyloid fibrils 365.1 Ure2p10–39 and full-length Ure2p fibrils 365.2 TTR105–115 fibrils 385.3 HET-s fibrils 385.4 Amylin fibrils 395.5 PrP fibrils 395.6 ccβ fibrils 405.7 α-synuclein fibrils 405.8 Calcitonin fibrils 416. Data relevant to various proposals regarding amyloid structure 416.1 β-helical models for amyloid fibrils 416.2 Amyloid fibrils as water-filled nanotubes 426.3 Domain swapping in amyloid fibrils 426.4 The parallel superpleated β-structure model 436.5 α-sheet structures in amyloid fibrils 437. Conclusions 448. Acknowledgments 469. References 46Solid-state nuclear magnetic resonance (NMR) measurements have made major contributions to our understanding of the molecular structures of amyloid fibrils, including fibrils formed by the β-amyloid peptide associated with Alzheimer's disease, by proteins associated with fungal prions, and by a variety of other polypeptides. Because solid-state NMR techniques can be used to determine interatomic distances (both intramolecular and intermolecular), place constraints on backbone and side-chain torsion angles, and identify tertiary and quaternary contacts, full molecular models for amyloid fibrils can be developed from solid-state NMR data, especially when supplemented by lower-resolution structural constraints from electron microscopy and other sources. In addition, solid-state NMR data can be used as experimental tests of various proposals and hypotheses regarding the mechanisms of amyloid formation, the nature of intermediate structures, and the common structural features within amyloid fibrils. This review introduces the basic experimental and conceptual principles behind solid-state NMR methods that are applicable to amyloid fibrils, reviews the information about amyloid structures that has been obtained to date with these methods, and discusses how solid-state NMR data provide insights into the molecular interactions that stabilize amyloid structures, the generic propensity of polypeptide chains to form amyloid fibrils, and a number of related issues that are of current interest in the amyloid field.

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10

Flynn, Jessica D., and Jennifer C. Lee. "Raman fingerprints of amyloid structures." Chemical Communications 54, no. 51 (2018): 6983–86. http://dx.doi.org/10.1039/c8cc03217c.

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11

Makshakova, Olga N., Liliya R. Bogdanova, Dzhigangir A. Faizullin, Elena A. Ermakova, and Yuriy F. Zuev. "Sulfated Polysaccharides as a Fighter with Protein Non-Physiological Aggregation: The Role of Polysaccharide Flexibility and Charge Density." International Journal of Molecular Sciences 24, no. 22 (November 12, 2023): 16223. http://dx.doi.org/10.3390/ijms242216223.

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Proteins can lose native functionality due to non-physiological aggregation. In this work, we have shown the power of sulfated polysaccharides as a natural assistant to restore damaged protein structures. Protein aggregates enriched by cross-β structures are a characteristic of amyloid fibrils related to different health disorders. Our recent studies demonstrated that model fibrils of hen egg white lysozyme (HEWL) can be disaggregated and renatured by some negatively charged polysaccharides. In the current work, using the same model protein system and FTIR spectroscopy, we studied the role of conformation and charge distribution along the polysaccharide chain in the protein secondary structure conversion. The effects of three carrageenans (κ, ι, and λ) possessing from one to three sulfate groups per disaccharide unit were shown to be different. κ-Carrageenan was able to fully eliminate cross-β structures and complete the renaturation process. ι-Carrageenan only initiated the formation of native-like β-structures in HEWL, retaining most of the cross-β structures. In contrast, λ-carrageenan even increased the content of amyloid cross-β structures. Furthermore, κ-carrageenan in rigid helical conformation loses its capability to restore protein native structures, largely increasing the amount of amyloid cross-β structures. Our findings create a platform for the design of novel natural chaperons to counteract protein unfolding.

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Hewetson, Aveline, Nazmul H. Khan, Matthew J. Dominguez, Hoa Quynh Do, R. E. Kusko, Collin G. Borcik, Daniel J. Rigden, et al. "Maturation of the functional mouse CRES amyloid from globular form." Proceedings of the National Academy of Sciences 117, no. 28 (June 29, 2020): 16363–72. http://dx.doi.org/10.1073/pnas.2006887117.

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The epididymal lumen contains a complex cystatin-rich nonpathological amyloid matrix with putative roles in sperm maturation and sperm protection. Given our growing understanding for the biological function of this and other functional amyloids, the problem still remains: how functional amyloids assemble including their initial transition to early oligomeric forms. To examine this, we developed a protocol for the purification of nondenatured mouse CRES, a component of the epididymal amyloid matrix, allowing us to examine its assembly to amyloid under conditions that may mimic those in vivo. Herein we use X-ray crystallography, solution-state NMR, and solid-state NMR to follow at the atomic level the assembly of the CRES amyloidogenic precursor as it progressed from monomeric folded protein to an advanced amyloid. We show the CRES monomer has a typical cystatin fold that assembles into highly branched amyloid matrices, comparable to those in vivo, by forming β-sheet assemblies that our data suggest occur via two distinct mechanisms: a unique conformational switch of a highly flexible disulfide-anchored loop to a rigid β-strand and by traditional cystatin domain swapping. Our results provide key insight into our understanding of functional amyloid assembly by revealing the earliest structural transitions from monomer to oligomer and by showing that some functional amyloid structures may be built by multiple and distinctive assembly mechanisms.

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Balobanov, Vitalii, Rita Chertkova, Anna Egorova, Dmitry Dolgikh, Valentina Bychkova, and Mikhail Kirpichnikov. "The Kinetics of Amyloid Fibril Formation by de Novo Protein Albebetin and Its Mutant Variants." Biomolecules 10, no. 2 (February 5, 2020): 241. http://dx.doi.org/10.3390/biom10020241.

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Engineering of amyloid structures is one of the new perspective areas of protein engineering. Studying the process of amyloid formation can help find ways to manage it in the interests of medicine and biotechnology. One of the promising candidates for the structural basis of artificial functional amyloid fibrils is albebetin (ABB), an artificial protein engineered under the leadership of O.B. Ptitsyn. Various aspects of the amyloid formation of this protein and some methods for controlling this process are investigated in this paper. Four stages of amyloid fibrils formation by this protein from the first non-fibrillar aggregates to mature fibrils and large micron-sized complexes have been described in detail. Dependence of albebetin amyloids formation on external conditions and some mutations also have been described. The introduction of similar point mutations in the two structurally identical α-β-β motifs of ABB lead to different amiloidogenesis kinetics. The inhibitory effect of a disulfide bond and high pH on amyloid fibrils formation, that can be used to control this process, was shown. The results of this work are a good basis for the further design and use of ABB-based amyloid constructs.

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LeVine, Harry. "Thioflavine T interaction with amyloid β-sheet structures." Amyloid 2, no. 1 (January 1995): 1–6. http://dx.doi.org/10.3109/13506129509031881.

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Fändrich, Marcus, Matthias Schmidt, and Nikolaus Grigorieff. "Recent progress in understanding Alzheimer's β-amyloid structures." Trends in Biochemical Sciences 36, no. 6 (June 2011): 338–45. http://dx.doi.org/10.1016/j.tibs.2011.02.002.

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Wickner, Reed B., Herman K. Edskes, David A. Bateman, Amy C. Kelly, Anton Gorkovskiy, Yaron Dayani, and Albert Zhou. "Amyloid diseases of yeast: prions are proteins acting as genes." Essays in Biochemistry 56 (August 18, 2014): 193–205. http://dx.doi.org/10.1042/bse0560193.

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The unusual genetic properties of the non-chromosomal genetic elements [URE3] and [PSI+] led to them being identified as prions (infectious proteins) of Ure2p and Sup35p respectively. Ure2p and Sup35p, and now several other proteins, can form amyloid, a linear ordered polymer of protein monomers, with a part of each molecule, the prion domain, forming the core of this β-sheet structure. Amyloid filaments passed to a new cell seed the conversion of the normal form of the protein into the same amyloid form. The cell's phenotype is affected, usually from the deficiency of the normal form of the protein. Solid-state NMR studies indicate that the yeast prion amyloids are in-register parallel β-sheet structures, in which each residue (e.g. Asn35) forms a row along the filament long axis. The favourable interactions possible for aligned identical hydrophilic and hydrophobic residues are believed to be the mechanism for propagation of amyloid conformation. Thus, just as DNA mediates inheritance by templating its own sequence, these proteins act as genes by templating their conformation. Distinct isolates of a given prion have different biological properties, presumably determined by differences between the amyloid structures. Many lines of evidence indicate that the Saccharomyces cerevisiae prions are pathological disease agents, although the example of the [Het-s] prion of Podospora anserina shows that a prion can have beneficial aspects.

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Okumura, Hisashi, and Satoru G. Itoh. "Molecular Dynamics Simulation Studies on the Aggregation of Amyloid-β Peptides and Their Disaggregation by Ultrasonic Wave and Infrared Laser Irradiation." Molecules 27, no. 8 (April 12, 2022): 2483. http://dx.doi.org/10.3390/molecules27082483.

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Alzheimer’s disease is understood to be caused by amyloid fibrils and oligomers formed by aggregated amyloid-β (Aβ) peptides. This review article presents molecular dynamics (MD) simulation studies of Aβ peptides and Aβ fragments on their aggregation, aggregation inhibition, amyloid fibril conformations in equilibrium, and disruption of the amyloid fibril by ultrasonic wave and infrared laser irradiation. In the aggregation of Aβ, a β-hairpin structure promotes the formation of intermolecular β-sheet structures. Aβ peptides tend to exist at hydrophilic/hydrophobic interfaces and form more β-hairpin structures than in bulk water. These facts are the reasons why the aggregation is accelerated at the interface. We also explain how polyphenols, which are attracting attention as aggregation inhibitors of Aβ peptides, interact with Aβ. An MD simulation study of the Aβ amyloid fibrils in equilibrium is also presented: the Aβ amyloid fibril has a different structure at one end from that at the other end. The amyloid fibrils can be destroyed by ultrasonic wave and infrared laser irradiation. The molecular mechanisms of these amyloid fibril disruptions are also explained, particularly focusing on the function of water molecules. Finally, we discuss the prospects for developing treatments for Alzheimer’s disease using MD simulations.

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Gorman, Paul M., and Avijit Chakrabartty. "Alzheimer β-amyloid peptides: Structures of amyloid fibrils and alternate aggregation products." Biopolymers 60, no. 5 (2001): 381. http://dx.doi.org/10.1002/1097-0282(2001)60:5<381::aid-bip10173>3.0.co;2-u.

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Chimon, Sandra, Medhat A. Shaibat, Christopher R. Jones, Diana C. Calero, Buzulagu Aizezi, and Yoshitaka Ishii. "Evidence of fibril-like β-sheet structures in a neurotoxic amyloid intermediate of Alzheimer's β-amyloid." Nature Structural & Molecular Biology 14, no. 12 (December 2007): 1157–64. http://dx.doi.org/10.1038/nsmb1345.

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Willem, Michael, and Marcus Fändrich. "A molecular view of human amyloid-β folds." Science 375, no. 6577 (January 14, 2022): 147–48. http://dx.doi.org/10.1126/science.abn5428.

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Daskalov, Asen, Denis Martinez, Virginie Coustou, Nadia El Mammeri, Mélanie Berbon, Loren B. Andreas, Benjamin Bardiaux, et al. "Structural and molecular basis of cross-seeding barriers in amyloids." Proceedings of the National Academy of Sciences 118, no. 1 (December 21, 2020): e2014085118. http://dx.doi.org/10.1073/pnas.2014085118.

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Neurodegenerative disorders are frequently associated with β-sheet-rich amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behavior and distinct pathophenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungusPodospora anserinarepresents a model system to study the fundamental properties of prion amyloids. Here, we report the amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two amyloids, sharing only 17% sequence identity, have nearly identical β-solenoid folds but lack cross-seeding ability in vivo, indicating that prion specificity can differ in extremely similar amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrier in vivo between HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an amyloid fold. Our work redefines the conceptual boundaries of prion strain and sheds light on key molecular features concerning an important class of pathogenic agents.

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Roterman, Irena, Katarzyna Stapor, and Leszek Konieczny. "Secondary Structure in Amyloids in Relation to Their Wild Type Forms." International Journal of Molecular Sciences 24, no. 1 (December 21, 2022): 154. http://dx.doi.org/10.3390/ijms24010154.

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The amyloid structures and their wild type forms, available in the PDB database, provide the basis for comparative analyses. Globular proteins are characterised by a 3D spatial structure, while a chain in any amyloid fibril has a 2D structure. Another difference lies in the structuring of the hydrogen bond network. Amyloid forms theoretically engage all the NH and C=O groups of the peptide bonds in a chain with two hydrogen bonds each. In addition, the hydrogen bond network is highly ordered—as perpendicular to the plane of the chain. The β-structure segments provide the hydrogen bond system with an anti-parallel system. The folds appearing in the rectilinear propagation of the segment with the β-structure are caused by just by one of the residues in the sequence—residues with a Rα-helical or Lα-helical conformation. The antiparallel system of the hydrogen bonds in the β-structure sections at the site of the amino acid with a Rα- or Lα-helical conformation changes into a parallel system locally. This system also ensures that the involvement of the C=O and H-N groups in the construction of the interchain hydrogen bond, while maintaining a perpendicular orientation towards the plane of the chain. Conformational analysis at the level of the Phi and Psi angles indicates the presence of the conditions for the structures observed in the amyloids. The specificity of amyloid structures with the dominant conformation expressed as |Psi| = |Phi| reveals the system of organisation present in amyloid fibrils. The Phi, Psi angles, as present in this particular structure, transformed to form |Psi| = |Phi| appear to be ordered co-linearly. Therefore, the calculation of the correlation coefficient may express the distribution around this idealised localisation on the Ramachandran map. Additionally, when the outstanding points are eliminated, the part of amyloid chain can be classified as fulfilling the defined conditions. In addition, the presentation of the chain structure using geometric parameters, V-angle—the angle between the planes of the adjacent peptide bonds (angle versus the virtual axis Cα-Cα) and the radius of the curvature R, depending on the size of the angle V, allows for a quantitative assessment of changes during amyloid transformation.

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Serpell, Louise. "Amyloid structure." Essays in Biochemistry 56 (August 18, 2014): 1–10. http://dx.doi.org/10.1042/bse0560001.

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Amyloid fibrils are formed by numerous proteins and peptides that share little sequence homology. The structures formed are highly ordered and extremely stable, being composed of β-sheet structure and stabilized along their length by hydrogen bonding. The fibrils are formed by several protofilaments that wind around one another in rope-like structures, lending further strength and stability to the resulting fibres. The fact that so many proteins and peptides form amyloid structures under suitable conditions, seems to suggest that the sequence of the precursor is unimportant. However, it is now clear that side chains play a central role in forming interactions between several β-sheets to further stabilize and regulate the structures. The primary sequence plays a central role in determining the rate of fibril formation, the stability of the resulting structure to degradation and the final morphology of the fibrils. The side chains regulate the elongation and growth, and also the lateral association of the protofilament and fibrils, having a significant impact on the final architecture.

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Urban, Jennifer M., Janson Ho, Gavin Piester, Riqiang Fu, and Bradley L. Nilsson. "Rippled β-Sheet Formation by an Amyloid-β Fragment Indicates Expanded Scope of Sequence Space for Enantiomeric β-Sheet Peptide Coassembly." Molecules 24, no. 10 (May 23, 2019): 1983. http://dx.doi.org/10.3390/molecules24101983.

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In 1953, Pauling and Corey predicted that enantiomeric β-sheet peptides would coassemble into so-called “rippled” β-sheets, in which the β-sheets would consist of alternating l- and d-peptides. To date, this phenomenon has been investigated primarily with amphipathic peptide sequences composed of alternating hydrophilic and hydrophobic amino acid residues. Here, we show that enantiomers of a fragment of the amyloid-β (Aβ) peptide that does not follow this sequence pattern, amyloid-β (16–22), readily coassembles into rippled β-sheets. Equimolar mixtures of enantiomeric amyloid-β (16–22) peptides assemble into supramolecular structures that exhibit distinct morphologies from those observed by self-assembly of the single enantiomer pleated β-sheet fibrils. Formation of rippled β-sheets composed of alternating l- and d-amyloid-β (16–22) is confirmed by isotope-edited infrared spectroscopy and solid-state NMR spectroscopy. Sedimentation analysis reveals that rippled β-sheet formation by l- and d-amyloid-β (16–22) is energetically favorable relative to self-assembly into corresponding pleated β-sheets. This work illustrates that coassembly of enantiomeric β-sheet peptides into rippled β-sheets is not limited to peptides with alternating hydrophobic/hydrophilic sequence patterns, but that a broader range of sequence space is available for the design and preparation of rippled β-sheet materials.

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TJERNBERG, Lars O., Agneta TJERNBERG, Niklas BARK, Yuan SHI, Bela P. RUZSICSKA, Zimei BU, Johan THYBERG, and David J. E. CALLAWAY. "Assembling amyloid fibrils from designed structures containing a significant amyloid β-peptide fragment." Biochemical Journal 366, no. 1 (August 15, 2002): 343–51. http://dx.doi.org/10.1042/bj20020229.

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The amyloid plaque, consisting of amyloid β-peptide (Aβ) fibrils surrounded by dystrophic neurites, is an invariable feature of Alzheimer's disease. The determination of the molecular structure of Aβ fibrils is a significant goal that may lead to the structure-based design of effective therapeutics for Alzheimer's disease. Technical challenges have thus far rendered this goal impossible. In the present study, we develop an alternative methodology. Rather than determining the structure directly, we design conformationally constrained peptides and demonstrate that only certain ‘bricks’ can aggregate into fibrils morphologically identical to Aβ fibrils. The designed peptides include variants of a decapeptide fragment of Aβ, previously shown to be one of the smallest peptides that (1) includes a pentapeptide sequence necessary for Aβ—Aβ binding and aggregation and (2) can form fibrils indistinguishable from those formed by full-length Aβ. The secondary structure of these bricks is monitored by CD spectroscopy, and electron microscopy is used to study the morphology of the aggregates formed. We then made various residue deletions and substitutions to determine which structural features are essential for fibril formation. From the constraints, statistical analysis of side-chain pair correlations in β-sheets and experimental data, we deduce a detailed model of the peptide strand alignment in fibrils formed by these bricks. Our results show that the constrained decapeptide dimers rapidly form an intramolecular, antiparallel β-sheet and polymerize into amyloid fibrils at low concentrations. We suggest that the formation of an exposed β-sheet (e.g. an Aβ dimer formed by interaction in the decapeptide region) could be a rate-limiting step in fibril formation. A theoretical framework that explains the results is presented in parallel with the data.

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Jara-Moreno, Daniela, Ana L. Riveros, Andrés Barriga, Marcelo J. Kogan, and Carla Delporte. "Inhibition of β-amyloid Aggregation of Ugni molinae Extracts." Current Pharmaceutical Design 26, no. 12 (May 6, 2020): 1365–76. http://dx.doi.org/10.2174/1381612826666200113160840.

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The β-amyloid peptide (1-42) is a molecule capable of aggregating into neurotoxic structures that have been implicated as potential etiological factors of Alzheimer's Disease. The aim of this study was to evaluate the inhibition of β-amyloid aggregation of ethyl acetate and ethanolic extracts obtained from Ugni molinae leaves on neurotoxic actions of β-amyloid aggregates. Chemical analyses were carried out with the extracts in order to determine their phenolic profile and its quantification. Both extracts showed a tendency to reduce neuronal deaths caused by β-amyloid. This tendency was inversely proportional to the evaluated concentrations. Moreover, the effect of EAE and ETE on β-amyloid aggregation was studied by fluorimetric T Thioflavin assay and transmission electronic microscopy (TEM); the extracts showed a modulation in the aggregation process. Partly, it is believed that these effects can be attributed to the polyphenolic compounds present in the extracts.

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Tavanti, Francesco, Alfonso Pedone, and Maria Cristina Menziani. "Disclosing the Interaction of Gold Nanoparticles with Aβ(1–40) Monomers through Replica Exchange Molecular Dynamics Simulations." International Journal of Molecular Sciences 22, no. 1 (December 22, 2020): 26. http://dx.doi.org/10.3390/ijms22010026.

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Amyloid-β aggregation is one of the principal causes of amyloidogenic diseases that lead to the loss of neuronal cells and to cognitive impairments. The use of gold nanoparticles treating amyloidogenic diseases is a promising approach, because the chemistry of the gold surface can be tuned in order to have a specific binding, obtaining effective tools to control the aggregation. In this paper, we show, by means of Replica Exchange Solute Tempering Molecular Simulations, how electrostatic interactions drive the absorption of Amyloid-β monomers onto citrates-capped gold nanoparticles. Importantly, upon binding, amyloid monomers show a reduced propensity in forming β-sheets secondary structures that are characteristics of mature amyloid fibrils.

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Pellegrino, S., N. Tonali, E. Erba, J. Kaffy, M. Taverna, A. Contini, M. Taylor, D. Allsop, M. L. Gelmi, and S. Ongeri. "β-Hairpin mimics containing a piperidine–pyrrolidine scaffold modulate the β-amyloid aggregation process preserving the monomer species." Chemical Science 8, no. 2 (2017): 1295–302. http://dx.doi.org/10.1039/c6sc03176e.

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Westlind-Danielsson, Anita, and Gunnel Arnerup. "Spontaneous in Vitro Formation of Supramolecular β-Amyloid Structures, “βamy Balls”, by β-Amyloid 1−40 Peptide†." Biochemistry 40, no. 49 (December 2001): 14736–43. http://dx.doi.org/10.1021/bi010375c.

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Murakoshi, Yuko, Tsuyoshi Takahashi, and Hisakazu Mihara. "Modification of a Small β-Barrel Protein, To Give Pseudo-Amyloid Structures, Inhibits Amyloid β-Peptide Aggregation." Chemistry - A European Journal 19, no. 14 (February 1, 2013): 4525–31. http://dx.doi.org/10.1002/chem.201202762.

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Almeida, Zaida L., and Rui M. M. Brito. "Amyloid Disassembly: What Can We Learn from Chaperones?" Biomedicines 10, no. 12 (December 17, 2022): 3276. http://dx.doi.org/10.3390/biomedicines10123276.

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Protein aggregation and subsequent accumulation of insoluble amyloid fibrils with cross-β structure is an intrinsic characteristic of amyloid diseases, i.e., amyloidoses. Amyloid formation involves a series of on-pathway and off-pathway protein aggregation events, leading to mature insoluble fibrils that eventually accumulate in multiple tissues. In this cascade of events, soluble oligomeric species are formed, which are among the most cytotoxic molecular entities along the amyloid cascade. The direct or indirect action of these amyloid soluble oligomers and amyloid protofibrils and fibrils in several tissues and organs lead to cell death in some cases and organ disfunction in general. There are dozens of different proteins and peptides causing multiple amyloid pathologies, chief among them Alzheimer’s, Parkinson’s, Huntington’s, and several other neurodegenerative diseases. Amyloid fibril disassembly is among the disease-modifying therapeutic strategies being pursued to overcome amyloid pathologies. The clearance of preformed amyloids and consequently the arresting of the progression of organ deterioration may increase patient survival and quality of life. In this review, we compiled from the literature many examples of chemical and biochemical agents able to disaggregate preformed amyloids, which have been classified as molecular chaperones, chemical chaperones, and pharmacological chaperones. We focused on their mode of action, chemical structure, interactions with the fibrillar structures, morphology and toxicity of the disaggregation products, and the potential use of disaggregation agents as a treatment option in amyloidosis.

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Tycko, Robert, Kimberly L. Sciarretta, Joseph P. R. O. Orgel, and Stephen C. Meredith. "Evidence for Novel β-Sheet Structures in Iowa Mutant β-Amyloid Fibrils." Biochemistry 48, no. 26 (July 7, 2009): 6072–84. http://dx.doi.org/10.1021/bi9002666.

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Zhizhin, Gennadiy Vladimirovich. "On the Possible Spatial Structures of the β-Amyloid." International Journal of Applied Research on Public Health Management 7, no. 1 (January 2022): 1–8. http://dx.doi.org/10.4018/ijarphm.290380.

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Spatial models of the β - structures of protein molecules, forming layers of amino acids, in principle, of unlimited length for both antiparallel and parallel conformation have been constructed. It is shown that the simplified flat Pauling models do not reflect the spatial structure of these layers. Using the recently developed theory of higher-dimensional polytopic prismahedrons, models of the volumetric filling of space with amino acid molecules are constructed. The constructed models for the first time mathematically describe the native structures of globular proteins.

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Pham, Johnny D., Nicholas Chim, Celia W. Goulding, and James S. Nowick. "Structures of Oligomers of a Peptide from β-Amyloid." Journal of the American Chemical Society 135, no. 33 (August 8, 2013): 12460–67. http://dx.doi.org/10.1021/ja4068854.

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Muvva, Charuvaka, Natarajan Arul Murugan, and Venkatesan Subramanian. "Assessment of Amyloid Forming Tendency of Peptide Sequences from Amyloid Beta and Tau Proteins Using Force-Field, Semi-Empirical, and Density Functional Theory Calculations." International Journal of Molecular Sciences 22, no. 6 (March 23, 2021): 3244. http://dx.doi.org/10.3390/ijms22063244.

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A wide variety of neurodegenerative diseases are characterized by the accumulation of protein aggregates in intraneuronal or extraneuronal brain regions. In Alzheimer’s disease (AD), the extracellular aggregates originate from amyloid-β proteins, while the intracellular aggregates are formed from microtubule-binding tau proteins. The amyloid forming peptide sequences in the amyloid-β peptides and tau proteins are responsible for aggregate formation. Experimental studies have until the date reported many of such amyloid forming peptide sequences in different proteins, however, there is still limited molecular level understanding about their tendency to form aggregates. In this study, we employed umbrella sampling simulations and subsequent electronic structure theory calculations in order to estimate the energy profiles for interconversion of the helix to β-sheet like secondary structures of sequences from amyloid-β protein (KLVFFA) and tau protein (QVEVKSEKLD and VQIVYKPVD). The study also included a poly-alanine sequence as a reference system. The calculated force-field based free energy profiles predicted a flat minimum for monomers of sequences from amyloid and tau proteins corresponding to an α-helix like secondary structure. For the parallel and anti-parallel dimer of KLVFFA, double well potentials were obtained with the minima corresponding to α-helix and β-sheet like secondary structures. A similar double well-like potential has been found for dimeric forms for the sequences from tau fibril. Complementary semi-empirical and density functional theory calculations displayed similar trends, validating the force-field based free energy profiles obtained for these systems.

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Folmert, Kristin, Malgorzata Broncel, Hans v. Berlepsch, Christopher Hans Ullrich, Mary-Ann Siegert, and Beate Koksch. "Inhibition of peptide aggregation by means of enzymatic phosphorylation." Beilstein Journal of Organic Chemistry 12 (November 18, 2016): 2462–70. http://dx.doi.org/10.3762/bjoc.12.240.

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As is the case in numerous natural processes, enzymatic phosphorylation can be used in the laboratory to influence the conformational populations of proteins. In nature, this information is used for signal transduction or energy transfer, but has also been shown to play an important role in many diseases like tauopathies or diabetes. With the goal of determining the effect of phosphorylation on amyloid fibril formation, we designed a model peptide which combines structural characteristics of α-helical coiled-coils and β-sheets in one sequence. This peptide undergoes a conformational transition from soluble structures into insoluble amyloid fibrils over time and under physiological conditions and contains a recognition motif for PKA (cAMP-dependent protein kinase) that enables enzymatic phosphorylation. We have analyzed the pathway of amyloid formation and the influence of enzymatic phosphorylation on the different states along the conformational transition from random-coil to β-sheet-rich oligomers to protofilaments and on to insoluble amyloid fibrils, and we found a remarkable directing effect from β-sheet-rich structures to unfolded structures in the initial growth phase, in which small oligomers and protofilaments prevail if the peptide is phosphorylated.

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Ábrahám, Ágnes, Flavio Massignan, Gergő Gyulai, Miklós Katona, Nóra Taricska, and Éva Kiss. "Comparative Study of the Solid-Liquid Interfacial Adsorption of Proteins in Their Native and Amyloid Forms." International Journal of Molecular Sciences 23, no. 21 (October 30, 2022): 13219. http://dx.doi.org/10.3390/ijms232113219.

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The adhesive properties of amyloid fibers are thought to play a crucial role in various negative and positive aggregation processes, the study of which might help in their understanding and control. Amyloids have been prepared from two proteins, lysozyme and β-lactoglobulin, as well as an Exendin-4 derivative miniprotein (E5). Thermal treatment was applied to form amyloids and their structure was verified by thioflavin T (ThT), 8-Anilino-1-naphthalenesulfonic acid (ANS) dye tests and electronic circular dichroism spectroscopy (ECD). Adsorption properties of the native and amyloid forms of the three proteins were investigated and compared using the mass-sensitive quartz crystal microbalance (QCM) technique. Due to the possible electrostatic and hydrophobic interactions, similar adsorbed amounts were found for the native or amyloid forms, while the structures of the adsorbed layers differed significantly. Native proteins formed smooth and dense adsorption layers. On the contrary, a viscoelastic, highly loose layer was formed in the presence of the amyloid forms, shown by increased motional resistance values determined by the QCM technique and also indicated by atomic force microscopy (AFM) and wettability measurements. The elongated structure and increased hydrophobicity of amyloids might contribute to this kind of aggregation.

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Pusara, Srdjan. "Molecular Dynamics Insights into the Aggregation Behavior of N-Terminal β-Lactoglobulin Peptides." International Journal of Molecular Sciences 25, no. 9 (April 25, 2024): 4660. http://dx.doi.org/10.3390/ijms25094660.

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β-lactoglobulin (BLG) forms amyloid-like aggregates at high temperatures, low pH, and low ionic strengths. At a pH below 2, BLG undergoes hydrolysis into peptides, with N-terminal peptides 1–33 and 1–52 being prone to fibrillization, forming amyloid-like fibrils. Due to their good mechanical properties, BLG amyloids demonstrate great potential for diverse applications, including biosensors, nanocomposites, and catalysts. Consequently, further studies are essential to comprehensively understand the factors governing the formation of BLG amyloid-like morphologies. In this study, all-atom molecular dynamics simulations were employed to explore the aggregation of N-terminal 1–33 and 1–52 BLG peptides under conditions of pH 2 and at 10 mM NaCl concentration. The simulations revealed that the peptides spontaneously assembled into aggregates of varying sizes. The aggregation process was enabled by the low charge of peptides and the presence of hydrophobic residues within them. As the peptides associated into aggregates, there was a concurrent increase in β-sheet structures and the establishment of hydrogen bonds, enhancing the stability of the aggregates. Notably, on average, 1–33 peptides formed larger aggregates compared to their 1–52 counterparts, while the latter exhibited a slightly higher content of β-sheets and higher cluster orderliness. The applied approach facilitated insights into the early stages of amyloid-like aggregation and molecular-level insight into the formation of β-sheets, which serve as nucleation points for further fibril growth.

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Sønderby, Thorbjørn Vincent, Zahra Najarzadeh, and Daniel Erik Otzen. "Functional Bacterial Amyloids: Understanding Fibrillation, Regulating Biofilm Fibril Formation and Organizing Surface Assemblies." Molecules 27, no. 13 (June 24, 2022): 4080. http://dx.doi.org/10.3390/molecules27134080.

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Functional amyloid is produced by many organisms but is particularly well understood in bacteria, where proteins such as CsgA (E. coli) and FapC (Pseudomonas) are assembled as functional bacterial amyloid (FuBA) on the cell surface in a carefully optimized process. Besides a host of helper proteins, FuBA formation is aided by multiple imperfect repeats which stabilize amyloid and streamline the aggregation mechanism to a fast-track assembly dominated by primary nucleation. These repeats, which are found in variable numbers in Pseudomonas, are most likely the structural core of the fibrils, though we still lack experimental data to determine whether the repeats give rise to β-helix structures via stacked β-hairpins (highly likely for CsgA) or more complicated arrangements (possibly the case for FapC). The response of FuBA fibrillation to denaturants suggests that nucleation and elongation involve equal amounts of folding, but protein chaperones preferentially target nucleation for effective inhibition. Smart peptides can be designed based on these imperfect repeats and modified with various flanking sequences to divert aggregation to less stable structures, leading to a reduction in biofilm formation. Small molecules such as EGCG can also divert FuBA to less organized structures, such as partially-folded oligomeric species, with the same detrimental effect on biofilm. Finally, the strong tendency of FuBA to self-assemble can lead to the formation of very regular two-dimensional amyloid films on structured surfaces such as graphite, which strongly implies future use in biosensors or other nanobiomaterials. In summary, the properties of functional amyloid are a much-needed corrective to the unfortunate association of amyloid with neurodegenerative disease and a testimony to nature’s ability to get the best out of a protein fold.

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Morris, Kyle L., Alison Rodger, Matthew R. Hicks, Maya Debulpaep, Joost Schymkowitz, Frederic Rousseau, and Louise C. Serpell. "Exploring the sequence–structure relationship for amyloid peptides." Biochemical Journal 450, no. 2 (February 15, 2013): 275–83. http://dx.doi.org/10.1042/bj20121773.

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Amyloid fibril formation is associated with misfolding diseases, as well as fulfilling a functional role. The cross-β molecular architecture has been reported in increasing numbers of amyloid-like fibrillar systems. The Waltz algorithm is able to predict ordered self-assembly of amyloidogenic peptides by taking into account the residue type and position. This algorithm has expanded the amyloid sequence space, and in the present study we characterize the structures of amyloid-like fibrils formed by three peptides identified by Waltz that form fibrils but not crystals. The structural challenge is met by combining electron microscopy, linear dichroism, CD and X-ray fibre diffraction. We propose structures that reveal a cross-β conformation with ‘steric-zipper’ features, giving insights into the role for side chains in peptide packing and stability within fibrils. The amenity of these peptides to structural characterization makes them compelling model systems to use for understanding the relationship between sequence, self-assembly, stability and structure of amyloid fibrils.

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Lee, Myungwoon, Tuo Wang, Olga V. Makhlynets, Yibing Wu, Nicholas F. Polizzi, Haifan Wu, Pallavi M. Gosavi, et al. "Zinc-binding structure of a catalytic amyloid from solid-state NMR." Proceedings of the National Academy of Sciences 114, no. 24 (May 31, 2017): 6191–96. http://dx.doi.org/10.1073/pnas.1706179114.

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Throughout biology, amyloids are key structures in both functional proteins and the end product of pathologic protein misfolding. Amyloids might also represent an early precursor in the evolution of life because of their small molecular size and their ability to self-purify and catalyze chemical reactions. They also provide attractive backbones for advanced materials. When β-strands of an amyloid are arranged parallel and in register, side chains from the same position of each chain align, facilitating metal chelation when the residues are good ligands such as histidine. High-resolution structures of metalloamyloids are needed to understand the molecular bases of metal–amyloid interactions. Here we combine solid-state NMR and structural bioinformatics to determine the structure of a zinc-bound metalloamyloid that catalyzes ester hydrolysis. The peptide forms amphiphilic parallel β-sheets that assemble into stacked bilayers with alternating hydrophobic and polar interfaces. The hydrophobic interface is stabilized by apolar side chains from adjacent sheets, whereas the hydrated polar interface houses the Zn2+-binding histidines with binding geometries unusual in proteins. Each Zn2+ has two bis-coordinated histidine ligands, which bridge adjacent strands to form an infinite metal–ligand chain along the fibril axis. A third histidine completes the protein ligand environment, leaving a free site on the Zn2+ for water activation. This structure defines a class of materials, which we call metal–peptide frameworks. The structure reveals a delicate interplay through which metal ions stabilize the amyloid structure, which in turn shapes the ligand geometry and catalytic reactivity of Zn2+.

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Lipke, Peter N., Marion Mathelié-Guinlet, Albertus Viljoen, and Yves F. Dufrêne. "A New Function for Amyloid-Like Interactions: Cross-Beta Aggregates of Adhesins form Cell-to-Cell Bonds." Pathogens 10, no. 8 (August 11, 2021): 1013. http://dx.doi.org/10.3390/pathogens10081013.

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Amyloid structures assemble through a repeating type of bonding called “cross-β”, in which identical sequences in many protein molecules form β-sheets that interdigitate through side chain interactions. We review the structural characteristics of such bonds. Single cell force microscopy (SCFM) shows that yeast expressing Als5 adhesin from Candida albicans demonstrate the empirical characteristics of cross-β interactions. These properties include affinity for amyloid-binding dyes, birefringence, critical concentration dependence, repeating structure, and inhibition by anti-amyloid agents. We present a model for how cross-β bonds form in trans between two adhering cells. These characteristics also apply to other fungal adhesins, so the mechanism appears to be an example of a new type of cell–cell adhesion.

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Diaferia, Carlo, Nicole Balasco, Davide Altamura, Teresa Sibillano, Enrico Gallo, Valentina Roviello, Cinzia Giannini, Giancarlo Morelli, Luigi Vitagliano, and Antonella Accardo. "Assembly modes of hexaphenylalanine variants as function of the charge states of their terminal ends." Soft Matter 14, no. 40 (2018): 8219–30. http://dx.doi.org/10.1039/c8sm01441h.

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Flores-Fernández, José, Vineet Rathod, and Holger Wille. "Comparing the Folds of Prions and Other Pathogenic Amyloids." Pathogens 7, no. 2 (May 4, 2018): 50. http://dx.doi.org/10.3390/pathogens7020050.

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Pathogenic amyloids are the main feature of several neurodegenerative disorders, such as Creutzfeldt–Jakob disease, Alzheimer’s disease, and Parkinson’s disease. High resolution structures of tau paired helical filaments (PHFs), amyloid-β(1-42) (Aβ(1-42)) fibrils, and α-synuclein fibrils were recently reported using cryo-electron microscopy. A high-resolution structure for the infectious prion protein, PrPSc, is not yet available due to its insolubility and its propensity to aggregate, but cryo-electron microscopy, X-ray fiber diffraction, and other approaches have defined the overall architecture of PrPSc as a 4-rung β-solenoid. Thus, the structure of PrPSc must have a high similarity to that of the fungal prion HET-s, which is part of the fungal heterokaryon incompatibility system and contains a 2-rung β-solenoid. This review compares the structures of tau PHFs, Aβ(1-42), and α-synuclein fibrils, where the β-strands of each molecule stack on top of each other in a parallel in-register arrangement, with the β-solenoid folds of HET-s and PrPSc.

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Lomarat, Pattamapan, Sirirat Chancharunee, Natthinee Anantachoke, Worawan Kitphati, Kittisak Sripha, and Nuntavan Bunyapraphatsara. "Bioactivity-guided Separation of the Active Compounds in Acacia Pennata Responsible for the Prevention of Alzheimer's Disease." Natural Product Communications 10, no. 8 (August 2015): 1934578X1501000. http://dx.doi.org/10.1177/1934578x1501000830.

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The objective of this study was to evaluate the health benefits of plants used in Thai food, specifically Acacia pennata Willd., in Alzheimer's prevention. A. pennata twigs strongly inhibited β-amyloid aggregation. Bioactivity-guided separation of the active fractions yielded six known compounds, tetracosane (1), 1-(heptyloxy)-octadecane (2), methyl tridecanoate (3), arborinone (4), confertamide A (5) and 4-hydroxy-1-methyl-pyrrolidin-2-carboxylic acid (6). The structures were determined by spectroscopic analysis. Biological testing revealed that tetracosane (1) was the most potent inhibitor of β-amyloid aggregation, followed by 1-(heptyloxy)-octadecane (2) with IC50 values of 0.4 and 12.3 μM. Methyl tridecanoate (3), arborinone (4) and 4-hydroxy-1-methyl-pyrrolidin-2-carboxylic acid (6) moderately inhibited β-amyloid aggregation. In addition, tetracosane (1) and methyl tridecanoate (3) weakly inhibited acetylcholinesterase (AChE). These results suggested that the effect of A pennata on Alzheimer's disease was likely due to the inhibition of β-amyloid aggregation. Thus A. pennata may be beneficial for Alzheimer's prevention.

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Cohen, Mark L., Chae Kim, Tracy Haldiman, Mohamed ElHag, Prachi Mehndiratta, Termsarasab Pichet, Frances Lissemore, et al. "Rapidly progressive Alzheimer’s disease features distinct structures of amyloid-β." Brain 138, no. 4 (February 13, 2015): 1009–22. http://dx.doi.org/10.1093/brain/awv006.

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Darling, April L., and James Shorter. "Atomic Structures of Amyloid-β Oligomers Illuminate a Neurotoxic Mechanism." Trends in Neurosciences 43, no. 10 (October 2020): 740–43. http://dx.doi.org/10.1016/j.tins.2020.07.006.

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Kim, S. T., and D. F. Weaver. "Theoretical studies on Alzheimer's disease: structures of β-amyloid aggregates." Journal of Molecular Structure: THEOCHEM 527, no. 1-3 (August 2000): 127–38. http://dx.doi.org/10.1016/s0166-1280(00)00485-1.

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Gallardo, Rodrigo, Neil A. Ranson, and Sheena E. Radford. "Amyloid structures: much more than just a cross-β fold." Current Opinion in Structural Biology 60 (February 2020): 7–16. http://dx.doi.org/10.1016/j.sbi.2019.09.001.

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Yagi-Utsumi, Maho, and Koichi Kato. "Conformational Variability of Amyloid-β and the Morphological Diversity of Its Aggregates." Molecules 27, no. 15 (July 26, 2022): 4787. http://dx.doi.org/10.3390/molecules27154787.

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Protein folding is the most fundamental and universal example of biomolecular self-organization and is characterized as an intramolecular process. In contrast, amyloidogenic proteins can interact with one another, leading to protein aggregation. The energy landscape of amyloid fibril formation is characterized by many minima for different competing low-energy structures and, therefore, is much more enigmatic than that of multiple folding pathways. Thus, to understand the entire energy landscape of protein aggregation, it is important to elucidate the full picture of conformational changes and polymorphisms of amyloidogenic proteins. This review provides an overview of the conformational diversity of amyloid-β (Aβ) characterized from experimental and theoretical approaches. Aβ exhibits a high degree of conformational variability upon transiently interacting with various binding molecules in an unstructured conformation in a solution, forming an α-helical intermediate conformation on the membrane and undergoing a structural transition to the β-conformation of amyloid fibrils. This review also outlines the structural polymorphism of Aβ amyloid fibrils depending on environmental factors. A comprehensive understanding of the energy landscape of amyloid formation considering various environmental factors will promote drug discovery and therapeutic strategies by controlling the fibril formation pathway and targeting the consequent morphology of aggregated structures.

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Journal articles on the topic 'Β-amyloid structures'

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