To see the other types of publications on this topic, follow the link: Oligomery.
Journal articles on the topic 'Oligomery'
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 'Oligomery.'
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
Faúndez, Eduardo I., and Mariom A. Carvajal. "Descripción del primer caso teratológico en un ejemplar de Esphalmenus silvestrii (Borelli) (Dermaptera: Pygidicranidae) de Isla Magdalena, Chile." REVISTA CHILENA DE ENTOMOLOGÍA 46, no. 4 (December 23, 2020): 745–48. http://dx.doi.org/10.35249/rche.46.4.20.21.
Full textAbstract:
First teratological case in the earwig Esphalmenus silvestrii (Borelli, 1902) is reported. The case belongs to an atrophy and oligomery unilateral with anarthrogenesis in the mesothoracic right leg. The case is discussed and illustrated. Additionally, this is the first record of E. silvestrii in Magdalena Island, Magellanes Region, Chile.
2
Thirunarayanan, Ayyavu, and Perumal Rajakumar. "Synthesis, photophysical and electrochemical properties of chiral and achiral thiadiazolophanes." RSC Adv. 4, no. 45 (2014): 23433–39. http://dx.doi.org/10.1039/c4ra02672a.
Full textAbstract:
One pot synthesis of chiral and achiral 2:2 oligomeric thiadiazolophane 1 and 3 and 3:3 oligomeric thiadiazolophane 2 and 4 with (S)-BINOL and methylene bis-naphthyl spacer unit has been achieved. The photophysical and electrochemical properties revealed higher degree of aggregation in 2:2 oligomor than 3:3 oligomer. Energy minimized calculations show that 3:3 oligomer has less heat of formation than 2:2 oligomer.
3
DECRAENE, L. P. RONSE, and E. F. SMETS. "The distribution and systematic relevance of the androecial character oligomery." Botanical Journal of the Linnean Society 118, no. 3 (July 1995): 193–247. http://dx.doi.org/10.1111/j.1095-8339.1995.tb00469.x.
Full text
4
DECRAENE, L., and E. SMETS. "The distribution and systematic relevance of the androecial character oligomery." Botanical Journal of the Linnean Society 118, no. 3 (July 1995): 193–247. http://dx.doi.org/10.1016/s0024-4074(05)80002-6.
Full text
5
Burford, Neil T., Tom Wehrman, Daniel Bassoni, Jonathan O’Connell, Martyn Banks, Litao Zhang, and Andrew Alt. "Identification of Selective Agonists and Positive Allosteric Modulators for µ- and δ-Opioid Receptors from a Single High-Throughput Screen." Journal of Biomolecular Screening 19, no. 9 (July 21, 2014): 1255–65. http://dx.doi.org/10.1177/1087057114542975.
Full textAbstract:
Hetero-oligomeric complexes of G protein–coupled receptors (GPCRs) may represent novel therapeutic targets exhibiting different pharmacology and tissue- or cell-specific site of action compared with receptor monomers or homo-oligomers. An ideal tool for validating this concept pharmacologically would be a hetero-oligomer selective ligand. We set out to develop and execute a 1536-well high-throughput screen of over 1 million compounds to detect potential hetero-oligomer selective ligands using a β-arrestin recruitment assay in U2OS cells coexpressing recombinant µ- and δ-opioid receptors. Hetero-oligomer selective ligands may bind to orthosteric or allosteric sites, and we might anticipate that the formation of hetero-oligomers may provide novel allosteric binding pockets for ligand binding. Therefore, our goal was to execute the screen in such a way as to identify positive allosteric modulators (PAMs) as well as agonists for µ, δ, and hetero-oligomeric receptors. While no hetero-oligomer selective ligands were identified (based on our selection criteria), this single screen did identify numerous µ- and δ-selective agonists and PAMs as well as nonselective agonists and PAMs. To our knowledge, these are the first µ- and δ-opioid receptor PAMs described in the literature.
6
Barton, Jeremy, D. Sebastian Arias, Chamani Niyangoda, Gustavo Borjas, Nathan Le, Saefallah Mohamed, and Martin Muschol. "Kinetic Transition in Amyloid Assembly as a Screening Assay for Oligomer-Selective Dyes." Biomolecules 9, no. 10 (September 27, 2019): 539. http://dx.doi.org/10.3390/biom9100539.
Full textAbstract:
Assembly of amyloid fibrils and small globular oligomers is associated with a significant number of human disorders that include Alzheimer’s disease, senile systemic amyloidosis, and type II diabetes. Recent findings implicate small amyloid oligomers as the dominant aggregate species mediating the toxic effects in these disorders. However, validation of this hypothesis has been hampered by the dearth of experimental techniques to detect, quantify, and discriminate oligomeric intermediates from late-stage fibrils, in vitro and in vivo. We have shown that the onset of significant oligomer formation is associated with a transition in thioflavin T kinetics from sigmoidal to biphasic kinetics. Here we showed that this transition can be exploited for screening fluorophores for preferential responses to oligomer over fibril formation. This assay identified crystal violet as a strongly selective oligomer-indicator dye for lysozyme. Simultaneous recordings of amyloid kinetics with thioflavin T and crystal violet enabled us to separate the combined signals into their underlying oligomeric and fibrillar components. We provided further evidence that this screening assay could be extended to amyloid-β peptides under physiological conditions. Identification of oligomer-selective dyes not only holds the promise of biomedical applications but provides new approaches for unraveling the mechanisms underlying oligomer versus fibril formation in amyloid assembly.
7
Wang, Yu, Karen S. L. Lam, Ming-hon Yau, and Aimin Xu. "Post-translational modifications of adiponectin: mechanisms and functional implications." Biochemical Journal 409, no. 3 (January 15, 2008): 623–33. http://dx.doi.org/10.1042/bj20071492.
Full textAbstract:
Adiponectin is an insulin-sensitizing adipokine with anti-diabetic, anti-atherogenic, anti-inflammatory and cardioprotective properties. This adipokine is secreted from adipocytes into the circulation as three oligomeric isoforms, including trimeric, hexameric and the HMW (high-molecular-mass) oligomeric complex consisting of at least 18 protomers. Each oligomeric isoform of adiponectin exerts distinct biological properties in its various target tissues. The HMW oligomer is the major active form mediating the insulin-sensitizing effects of adiponectin, whereas the central actions of this adipokine are attributed primarily to the hexameric and trimeric oligomers. In patients with Type 2 diabetes and coronary heart disease, circulating levels of HMW adiponectin are selectively decreased due to an impaired secretion of this oligomer from adipocytes. The biosynthesis of the adiponectin oligomers is a complex process involving extensive post-translational modifications. Hydroxylation and glycosylation of several conserved lysine residues in the collagenous domain of adiponectin are necessary for the intracellular assembly and stabilization of its high-order oligomeric structures. Secretion of the adiponectin oligomers is tightly controlled by a pair of molecular chaperones in the ER (endoplasmic reticulum), including ERp44 (ER protein of 44 kDa) and Ero1-Lα (ER oxidoreductase 1-Lα). ERp44 inhibits the secretion of adiponectin oligomers through a thiol-mediated retention. In contrast, Ero1-Lα releases HMW adiponectin trapped by ERp44. The PPARγ (peroxisome-proliferator-activated receptor γ) agonists thiazolidinediones selectively enhance the secretion of HMW adiponectin through up-regulation of Ero1-Lα. In the present review, we discuss the recent advances in our understanding of the structural and biological properties of the adiponectin oligomeric isoforms and highlight the role of post-translational modifications in regulating the biosynthesis of HMW adiponectin.
8
Bazaco, Raúl Blanco, José L. Segura, and Carlos Seoane. "Recent advances in the design, synthesis and study of covalent conjugated oligomer–C60 ensembles." Collection of Czechoslovak Chemical Communications 74, no. 6 (2009): 857–86. http://dx.doi.org/10.1135/cccc2008218.
Full textAbstract:
This review presents an overview of the most recent results in the field of conjugated oligomer covalently attached to the C60 sphere focusing mainly on donor–conjugated oligomer–C60 triads and conjugated oligomer–multifullerene materials. Well-defined monodisperse oligomers as new materials that exhibit interesting optoelectronic properties have been the subject of intense study during the last decade. In this regard, a huge amount of work has been devoted to the development of new synthetic strategies toward the synthesis of conjugated oligomeric materials with precise length and constitution and to their chemical functionalization in order to incorporate them into more complex molecular and supramolecular architectures. An important area of research in the field of conjugated oligomers involves the design and synthesis of donor–acceptor ensembles by combination of monodisperse π-conjugated oligomeric systems with C60 fullerene. Such hybrid systems have shown excited-state interactions making them excellent candidates for fundamental photophysical studies. In addition, these materials have found applications in the field of photovoltaic devices. A review with 70 references.
9
Thoms, Sven. "Import of proteins into peroxisomes: piggybacking to a new home away from home." Open Biology 5, no. 11 (November 2015): 150148. http://dx.doi.org/10.1098/rsob.150148.
Full textAbstract:
Peroxisomes are capable of importing folded and oligomeric proteins. However, it is a matter of dispute whether oligomer import by peroxisomes is the exception or the rule. Here, I argue for a clear distinction between homo-oligomeric proteins that are essentially peroxisomal, and dually localized hetero-oligomers that access the peroxisome by piggyback import, localizing there in limited number, whereas the majority remain in the cytosol. Homo-oligomeric proteins comprise the majority of all peroxisomal matrix proteins. There is evidence that binding by Pex5 in the cytosol can regulate their oligomerization state before import. The hetero-oligomer group is made up of superoxide dismutase and lactate dehydrogenase. These proteins have evolved mechanisms that render import inefficient and retain the majority of proteins in the cytosol.
10
Liu, Guang-Hui, Jing Qu, Anne E. Carmack, Hyun Bae Kim, Chang Chen, Hongmei Ren, Andrew J. Morris, Brian N. Finck, and Thurl E. Harris. "Lipin proteins form homo- and hetero-oligomers." Biochemical Journal 432, no. 1 (October 25, 2010): 65–76. http://dx.doi.org/10.1042/bj20100584.
Full textAbstract:
Lipin family members (lipin 1, 2 and 3) are bi-functional proteins that dephosphorylate PA (phosphatidic acid) to produce DAG (diacylglycerol) and act in the nucleus to regulate gene expression. Although other components of the triacylglycerol synthesis pathway can form oligomeric complexes, it is unknown whether lipin proteins also exist as oligomers. In the present study, using various approaches, we revealed that lipin 1 formed stable homo-oligomers with itself and hetero-oligomers with lipin 2/3. Both the N- and C-terminal regions of lipin 1 mediate its oligomerization in a head-to-head/tail-to-tail manner. We also show that lipin 1 subcellular localization can be influenced through oligomerization, and the individual lipin 1 monomers in the oligomer function independently in catalysing dephosphorylation of PA. The present study provides evidence that lipin proteins function as oligomeric complexes and that the three mammalian lipin isoforms can form combinatorial units.
11
Renaud, Justin, Abdulhrahman M. Alhazmi, and Paul M. Mayer. "Comparing the fragmentation chemistry of gas-phase adducts of poly(dimethylsiloxane) oligomers with metal and organic ions." Canadian Journal of Chemistry 87, no. 2 (February 2009): 453–59. http://dx.doi.org/10.1139/v08-184.
Full textAbstract:
Gas-phase ions of poly(dimethylsiloxane) oligomers were formed by electrospray ionization either by protonating them in solution with formic acid or by generating adducts of the oligomers with the metal ions Li+, Na+, K+, and Ag+ as well as with the organic cations NH4+, CH3CH2NH3+, and protonated glycine, aspartic acid, and 1,2-diphenylethylamine. The collision-induced fragmentation of the oligomeric ions was strongly dependent on the nature of the charging species. Ag+ adducts dissociated in a manner previously observed in secondary ion mass spectrometry experiments generating a series of linear and cyclic fragment ions, while Li+ adducts fragmented to form two ions: an adduct of the metal ion with the oligomer end-group and one with the remaining oligomer. Na+ and K+ adducts simply dissociate to form the bare metal ion. The organic species, to varying extents, transfer the proton to the oligomer to form a protonated poly(siloxane) ion. These protonated oligomers then dissociate at very low laboratory-frame collision energy along the siloxane backbone by loss of a silanol. These backbone fragments can then lose a methyl group to form a second series of fragment ions. Suggestions for probable mechanistic pathways for these processes are presented.
12
Long, Jaclyn S., Nigel J. Pyne, and Susan Pyne. "Lipid phosphate phosphatases form homo- and hetero-oligomers: catalytic competency, subcellular distribution and function." Biochemical Journal 411, no. 2 (March 27, 2008): 371–77. http://dx.doi.org/10.1042/bj20071607.
Full textAbstract:
Lipid phosphate phosphatases (LPP1–LPP3) have been topographically modelled as monomers (molecular mass of 31–36 kDa) composed of six transmembrane domains and with the catalytic site facing the extracellular side of the plasma membrane or the luminal side of intracellular membranes. The catalytic motif has three conserved domains, termed C1, C2 and C3. The C1 domain may be involved in substrate recognition, whereas C2 and C3 domains appear to participate in the catalytic dephosphorylation of the substrate. We have obtained three lines of evidence to demonstrate that LPPs exist as functional oligomers. First, we have used recombinant expression and immunoprecipitation analysis to demonstrate that LPP1, LPP2 and LPP3 form both homo- and hetero-oligomers. Secondly, large LPP oligomeric complexes that are catalytically active were isolated using gel-exclusion chromatography. Thirdly, we demonstrate that catalytically deficient guinea-pig FLAG-tagged H223L LPP1 mutant can form an oligomer with wild-type LPP1 and that wild-type LPP1 activity is preserved in the oligomer. These findings suggest that, in an oligomeric arrangement, the catalytic site of the wild-type LPP can function independently of the catalytic site of the mutant LPP. Finally, we demonstrate that endogenous LPP2 and LPP3 form homo- and hetero-oligomers, which differ in their subcellular localization and which may confer differing spatial regulation of phosphatidic acid and sphingosine 1-phosphate signalling.
13
Chase, Anna R., Ethan Laudermilch, Jimin Wang, Hideki Shigematsu, Takeshi Yokoyama, and Christian Schlieker. "Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1." Molecular Biology of the Cell 28, no. 21 (October 15, 2017): 2765–72. http://dx.doi.org/10.1091/mbc.e17-05-0281.
Full textAbstract:
TorsinA is an essential AAA+ ATPase requiring LAP1 or LULL1 as cofactors. The dynamics of the Torsin/cofactor system remain poorly understood, with previous models invoking Torsin/cofactor assemblies with fixed stoichiometries. Here we demonstrate that TorsinA assembles into homotypic oligomers in the presence of ATP. Torsin variants mutated at the “back” interface disrupt homo-oligomerization but still show robust ATPase activity in the presence of its cofactors. These Torsin mutants are severely compromised in their ability to rescue nuclear envelope defects in Torsin-deficient cells, suggesting that TorsinA homo-oligomers play a key role in vivo. Engagement of the oligomer by LAP1 triggers ATP hydrolysis and rapid complex disassembly. Thus the Torsin complex is a highly dynamic assembly whose oligomeric state is tightly controlled by distinctively localized cellular cofactors. Our discovery that LAP1 serves as a modulator of the oligomeric state of an AAA+ protein establishes a novel means of regulating this important class of oligomeric ATPases.
14
Schmid, J. A., H. Just, and H. H. Sitte. "Impact of oligomerization on the function of the human serotonin transporter." Biochemical Society Transactions 29, no. 6 (November 1, 2001): 732–36. http://dx.doi.org/10.1042/bst0290732.
Full textAbstract:
The formation of oligomeric structures has been proposed for a large number of membrane proteins, including G-protein-coupled receptors and ion channels. Biochemical studies employing gel filtration, cross-linking or co-immunoprecipitation techniques showed that the serotonin [5-hydroxytryptamine (5-HT)] transporter is also capable of forming oligomers. We investigated whether the human serotonin transporter (hSERT) can be visualized as an oligomer in the plasma membrane of intact cells. To test this working hypothesis, we generated fusion proteins of hSERT and spectral variants of green fluorescent protein [cyan and yellow fluorescent proteins (CFP and YFP, respectively)]. When expressed in HeLa or HEK-293 cells, the resulting fusion proteins (CFP-hSERT and YFP-hSERT) were inserted into the plasma membrane and were indistinguishable from wild-type hSERT on functional testing (5-HT uptake assays, inhibition of 5-HT uptake by blockers such as imipramine). Oligomers were visualized by fluorescence resonance energy transfer (FRET) microscopy in living cells using complementary methods. Interestingly, oligomerization was not confined to hSERT; FRET was also observed between CFP-and YFP-labelled rat γ-aminobutyric acid transporter. Gel filtration experiments showed that most of the protein was recovered as higher molecular weight complexes; almost no monomeric form was detected. This indicates that the homo-oligomeric form is the favoured state of hSERT in living cells. The formation of oligomers was not significantly affected by co-incubation with transporter substrates or blockers. Based on our observations, oligomer formation might not be essential for the physiological function of the transporter protein, the re-uptake of substrates. Furthermore, we conclude that constitutive oligomer formation might be a general property of Na+/Cl−-dependent neurotransmitter transporters.
15
Di Gennaro, Patrizia, Valentina Sabatini, Silvia Fallarini, Roberto Pagliarin, and Guido Sello. "Polyphenol Polymerization by an Alternative Oxidative Microbial Enzyme and Characterization of the Biological Activity of Oligomers." BioMed Research International 2018 (2018): 1–10. http://dx.doi.org/10.1155/2018/3828627.
Full textAbstract:
The recombinant catalase-peroxidase HPI from E. coli was used as an alternative enzyme in polymerization reactions for the production of (−) epicatechin oligomers and their biological activity was characterized. The enzyme was prepared in two forms: a purified and an immobilized form. Both were tested for their activity in oxidative polymerization reactions, and their stability and reusability were assessed. The polymerization reactions were followed by SEC-HPLC analyses, and the substrate was completely converted into one or more polymerization products depending on the reactions conditions. Results showed that the utilized conditions allowed for the isolation of some oligomers of different molecular weight: the oligomers containing 6 and 7 units of epicatechin substrate are the heaviest ones. Epicatechin was also used in reactions catalyzed by HRP in the same reaction conditions for comparison. In addition, one selected oligomer obtained by HPI enzyme catalysis was shown to act as in vitro inhibitor of tumor cell growth, like one oligomer deriving from epicatechin by HRP catalysis. These data confirm that epicatechin oligomeric form is more effective than its monomer in biological activity and suggest the use of HPI as an alternative enzyme in reactions for the production of epicatechin oligomers.
16
RAMSAY, Douglas, Elaine KELLETT, Mary McVEY, Stephen REES, and Graeme MILLIGAN. "Homo- and hetero-oligomeric interactions between G-protein-coupled receptors in living cells monitored by two variants of bioluminescence resonance energy transfer (BRET): hetero-oligomers between receptor subtypes form more efficiently than between less closely related sequences." Biochemical Journal 365, no. 2 (July 15, 2002): 429–40. http://dx.doi.org/10.1042/bj20020251.
Full textAbstract:
Homo- and hetero-oligomerization of G-protein-coupled receptors (GPCRs) were examined in HEK-293 cells using two variants of bioluminescence resonance energy transfer (BRET). BRET2 (a variant of BRET) offers greatly improved separation of the emission spectra of the donor and acceptor moieties compared with traditional BRET. Previously recorded homo-oligomerization of the human δ-opioid receptor was confirmed using BRET2. Homo-oligomerization of the κ-opioid receptor was observed using both BRET techniques. Both homo- and hetero-oligomers, containing both δ- and κ-opioid receptors, were unaffected by the presence of receptor ligands. BRET detection of opioid receptor homo- and hetero-oligomers required expression of 50000–100000 copies of the receptor energy acceptor construct per cell. The effectiveness of δ—κ-opioid receptor hetero-oligomer formation was as great as for homomeric interactions. The capacity of the two opioid receptors to form oligomeric complexes with the β2-adrenoceptor was also assessed. Although such interactions were detected, at least 250000 copies per cell of the energy acceptor were required. Requirement for high levels of receptor expression was equally pronounced in attempts to measure hetero-oligomer formation between the κ-opioid receptor and the thyrotropin-releasing hormone receptor-1. These studies indicate that constitutively formed homo- and hetero-oligomers of opioid receptor subtypes can be detected in living cells containing less than 100000 copies of the receptors. However, although hetero-oligomeric interactions between certain less closely related GPCRs can be detected, they appear to be of lower affinity than homo- or hetero-oligomers containing closely related sequences. Interactions recorded between certain GPCR family members in heterologous expression systems are likely to be artefacts of extreme levels of overexpression.
17
Larson, Megan E., Susan J. Greimel, Fatou Amar, Michael LaCroix, Gabriel Boyle, Mathew A. Sherman, Hallie Schley, et al. "Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits." Proceedings of the National Academy of Sciences 114, no. 23 (May 22, 2017): E4648—E4657. http://dx.doi.org/10.1073/pnas.1704698114.
Full textAbstract:
Mounting evidence indicates that soluble oligomeric forms of amyloid proteins linked to neurodegenerative disorders, such as amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major deleterious species for neuronal function in these diseases. Here, we found an abnormal accumulation of oligomeric αSyn species in AD brains by custom ELISA, size-exclusion chromatography, and nondenaturing/denaturing immunoblotting techniques. Importantly, the abundance of αSyn oligomers in human brain tissue correlated with cognitive impairment and reductions in synapsin expression. By overexpressing WT human αSyn in an AD mouse model, we artificially enhanced αSyn oligomerization. These bigenic mice displayed exacerbated Aβ-induced cognitive deficits and a selective decrease in synapsins. Following isolation of various soluble αSyn assemblies from transgenic mice, we found that in vitro delivery of exogenous oligomeric αSyn but not monomeric αSyn was causing a lowering in synapsin-I/II protein abundance. For a particular αSyn oligomer, these changes were either dependent or independent on endogenous αSyn expression. Finally, at a molecular level, the expression of synapsin genes SYN1 and SYN2 was down-regulated in vivo and in vitro by αSyn oligomers, which decreased two transcription factors, cAMP response element binding and Nurr1, controlling synapsin gene promoter activity. Overall, our results demonstrate that endogenous αSyn oligomers can impair memory by selectively lowering synapsin expression.
18
Eghiaian, Frederic, Thorsten Daubenfeld, Yann Quenet, Marieke van Audenhaege, Anne-Pascale Bouin, Guillaume van der Rest, Jeanne Grosclaude, and Human Rezaei. "Diversity in prion protein oligomerization pathways results from domain expansion as revealed by hydrogen/deuterium exchange and disulfide linkage." Proceedings of the National Academy of Sciences 104, no. 18 (April 18, 2007): 7414–19. http://dx.doi.org/10.1073/pnas.0607745104.
Full textAbstract:
The prion protein (PrP) propensity to adopt different structures is a clue to its biological role. PrP oligomers have been previously reported to bear prion infectivity or toxicity and were also found along the pathway of in vitro amyloid formation. In the present report, kinetic and structural analysis of ovine PrP (OvPrP) oligomerization showed that three distinct oligomeric species were formed in parallel, independent kinetic pathways. Only the largest oligomer gave rise to fibrillar structures at high concentration. The refolding of OvPrP into these different oligomers was investigated by analysis of hydrogen/deuterium exchange and introduction of disulfide bonds. These experiments revealed that, before oligomerization, separation of contacts in the globular part (residues 127–234) occurred between the S1–H1–S2 domain (residues 132–167) and the H2–H3 bundle (residues 174–230), implying a conformational change of the S2–H2 loop (residues 168–173). The type of oligomer to be formed depended on the site where the expansion of the OvPrP monomer was initiated. Our data bring a detailed insight into the earlier conformational changes during PrP oligomerization and account for the diversity of oligomeric entities. The kinetic and structural mechanisms proposed here might constitute a physicochemical basis of prion strain genesis.
19
Prots, Iryna, Janina Grosch, Razvan-Marius Brazdis, Katrin Simmnacher, Vanesa Veber, Steven Havlicek, Christian Hannappel, et al. "α-Synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies." Proceedings of the National Academy of Sciences 115, no. 30 (July 10, 2018): 7813–18. http://dx.doi.org/10.1073/pnas.1713129115.
Full textAbstract:
α-Synuclein (α-Syn) aggregation, proceeding from oligomers to fibrils, is one central hallmark of neurodegeneration in synucleinopathies. α-Syn oligomers are toxic by triggering neurodegenerative processes in in vitro and in vivo models. However, the precise contribution of α-Syn oligomers to neurite pathology in human neurons and the underlying mechanisms remain unclear. Here, we demonstrate the formation of oligomeric α-Syn intermediates and reduced axonal mitochondrial transport in human neurons derived from induced pluripotent stem cells (iPSC) from a Parkinson’s disease patient carrying an α-Syn gene duplication. We further show that increased levels of α-Syn oligomers disrupt axonal integrity in human neurons. We apply an α-Syn oligomerization model by expressing α-Syn oligomer-forming mutants (E46K and E57K) and wild-type α-Syn in human iPSC-derived neurons. Pronounced α-Syn oligomerization led to impaired anterograde axonal transport of mitochondria, which can be restored by the inhibition of α-Syn oligomer formation. Furthermore, α-Syn oligomers were associated with a subcellular relocation of transport-regulating proteins Miro1, KLC1, and Tau as well as reduced ATP levels, underlying axonal transport deficits. Consequently, reduced axonal density and structural synaptic degeneration were observed in human neurons in the presence of high levels of α-Syn oligomers. Together, increased dosage of α-Syn resulting in α-Syn oligomerization causes axonal transport disruption and energy deficits, leading to synapse loss in human neurons. This study identifies α-Syn oligomers as the critical species triggering early axonal dysfunction in synucleinopathies.
20
Eisenberg, David, Arthur Laganowsky, Cong Liu, Michael Sawaya, Julian Whitelegge, Minglei Zhao, Angela Soriaga, et al. "Structural Studies of the Amyloid State of Proteins." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C797. http://dx.doi.org/10.1107/s205327331409202x.
Full textAbstract:
Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. At the morphological level, these fibers appear similar and are termed "amyloid." We found that the adhesive segments of amyloid fibers are short protein sequences which form pairs of interdigitated, in-register beta sheets. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that in the neurodegenerative diseases, smaller, often transient and polymorphic oligomers are the toxic entities. We have identified a segment of the amyloid-forming protein, alphaB crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: beta-sheet-rich structure, cytotoxicity, and recognition by an anti-oligomer antibody. The X-ray-derived atomic structure of the oligomer reveals a cylindrical barrel, formed from six anti-parallel, out-of-register protein strands, which we term a cylindrin. The cylindrin structure is compatible with sequence segments from the Abeta protein of Alzheimer's disease and from other amyloid proteins. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers, and are distinct in structure from amyloid fibrils.
21
de Klerk, G. J., and D. Engelen. "Assembly of Agrostemma githago (corn-cockle) storage proteins and their precursor proteins into oligomers." Biochemical Journal 230, no. 1 (August 15, 1985): 269–72. http://dx.doi.org/10.1042/bj2300269.
Full textAbstract:
The major fraction of seed storage proteins of Agrostemma githago (corn-cockle), a non-leguminous dicot, occurs as material with S20,w values of approximately 11S and approximately 2S, and a minor fraction as oligomers with S20,w values of approximately 6.5S. The 11S proteins are of the legumin type and consist of disulphide-linked α- and β-subunits of Mr approximately 39 000 and approximately 23 000 respectively. The oligomeric assembly of the precursor polypeptides of the 11S proteins was examined. The approximately 65 000-Mr precursor polypeptides of two 11S proteins, which consist of 38 000-25 000-Mr subunits and 36 000-22 000-Mr subunits respectively, were assembled into oligomers of approximately 7S and subsequently cleaved. Thereafter the 11S oligomer was formed. The 88 000-Mr precursor of a third 11S protein, which consists of 41 000-23 000-Mr subunits, was assembled into an approximately 8S oligomer and then cleaved, yielding two disulphide-linked intermediates of Mr 59 000 and 24 000. Thereafter, the 11S oligomer was formed. Processing of the 59 000-Mr to the 41 000-Mr polypeptide occurred both in the 8S and in the 11S form.
22
Dekker, J., A. van der Ende, P. H. Aelmans, and G. J. Strous. "Rat gastric mucin is synthesized and secreted exclusively as filamentous oligomers." Biochemical Journal 279, no. 1 (October 1, 1991): 251–56. http://dx.doi.org/10.1042/bj2790251.
Full textAbstract:
Oligomeric gastric mucin was isolated from the fundic part of the rat stomach. Previously we have shown by biochemical analysis that this oligomeric mucin consists of disulphide-linked homo-oligomers, which contain no other covalently attached proteins [Dekker, Aelmans & Strous (1991) Biochem. J. 277, 423-427]. Electron-microscopic images of the oligomeric mucin revealed a heterogenous population of long filamentous molecules of 300-3000 nm length. After reduction and carboxymethylation the monomeric mucins displayed a length distribution with a single peak at about 279 nm. Length-distribution analysis of oligomeric molecules with length up to 1000 nm revealed three subpopulations with one, two or three times the length of the monomeric mucin. The oligomers displayed small globular domains of about 15 nm, which were equally spaced along the molecule's length. As the distance between these globular domains was similar to the monomer length, these domains most likely indicate attachment sites of the monomers. These results show that the mucin monomers attached end-to-end in the oligomer. Biosynthesis of the mucin oligomers was studied by labelling of stomach explants in vitro with [35S]methionine, [3H]galactose or [35S]sulphate and subsequent immunoprecipitation of the mucin with a specific antiserum. Analysis by electrophoresis and gel filtration revealed that the oligomerization takes place by formation of disulphide bonds between the 300 kDa mucin precursors. The mucin was exclusively synthesized and secreted as fully glycosylated oligomers, as neither precursor proteins nor monomeric mucin were detected in the culture medium. A model for the biosynthesis of rat gastric mucin is proposed in which the filamentous mucin monomers are linked end-to-end by disulphide bonds.
23
Harrison, R. A. "Preliminary characterization of the multiple forms of ram sperm hyaluronidase." Biochemical Journal 252, no. 3 (June 15, 1988): 875–82. http://dx.doi.org/10.1042/bj2520875.
Full textAbstract:
An investigation was made of the inter-relationships and characteristics of various hyaluronidase forms isolated from ram spermatozoa. They were shown to be members of an oligomeric series, apparently formed by intermolecular disulphide cross-linking. Two monomer species were detected, alpha (Mr 89,600) and beta (Mr 81,200). Although the alpha species predominated, the two were evenly distributed throughout the oligomer population, and they shared antigenic determinants; the beta species did not arise from the alpha species as a result of catabolism following cell disruption. The oligomeric series was of the form [Hyal]n, where n = 1, 2, 4, 5, 6, 7 etc.; no trimer was detectable. Though essentially cationic, part of the hyaluronidase population also had anionic characteristics, probably due to oxidation of free thiol groups. In the anionic subpopulation tetramers and higher oligomers predominated, whereas the non-anionic subpopulation was composed of monomers, dimers and tetramers. The pH optimum of the monomer was 4.3 in 0.2 M-NaCl/0.1 M-sodium citrate, whereas that of the anionic oligomers was 4.9. Both serum albumin and polylysine stimulated enzyme activity at pH 4.0 in the absence of NaCl; polylysine was particularly effective. NaCl diminished the stimulatory effects, and essentially suppressed them above the pH optimum. The specific activities of different oligomer populations were the same as that of the monomer, and conversion of oligomers into monomer by reduction had likewise no effect upon the specific activity. Low concentrations of poly(vinyl alcohol), poly(ethylene glycol) or polyvinylpyrrolidone stabilized soluble hyaluronidase activity by preventing the enzyme's binding to surfaces; solutions of anionic oligomers were further stabilized by NaCl. Enzyme preparations were stable for several months frozen in the presence of poly(vinyl alcohol) and salt.
24
Oliva, A., H. Armas, and J. B. Fariña. "HPLC determination of polyethylene glycol 400 in urine: oligomeric profile in healthy and celiac disease subjects." Clinical Chemistry 40, no. 8 (August 1, 1994): 1571–74. http://dx.doi.org/10.1093/clinchem/40.8.1571.
Full textAbstract:
Abstract The absorption of orally administered polyethylene glycol (PEG) has been used to assess intestinal permeability. We describe a simple HPLC technique to determine the oligomeric profile of PEG excreted in urine. We measured the total (%) PEG excreted in 6 h and the ratio of the four smallest oligomers to the three largest oligomers (expressed as mean percentages). The proposed method differentiates distinct groups of subjects with varying degrees of intestinal permeability detected by intestinal biopsy. The percent of PEG excreted and the oligomer ratio values for healthy subjects were, respectively, 30.1 +/- 3.87 and 0.35 +/- 0.03; for celiac patients on a gluten-free diet, 24.5 +/- 6.65 and 0.45 +/- 0.16; and for celiac patients, 15.0 +/- 5.93 and 1.12 +/- 0.55.
25
Wako, Hiroshi, and Shigeru Endo. "ProMode-Oligomer: Database of Normal Mode Analysis in Dihedral Angle Space for a Full-Atom System of Oligomeric Proteins." Open Bioinformatics Journal 6, no. 1 (February 21, 2012): 9–19. http://dx.doi.org/10.2174/1875036201206010009.
Full textAbstract:
The database ProMode-Oligomer (http://promode.socs.waseda.ac.jp/promode_oligomer) was constructed by collecting normal-mode-analysis (NMA) results for oligomeric proteins including protein-protein complexes. As in the ProMode database developed earlier for monomers and individual subunits of oligomers (Bioinformatics vol. 20, pp. 2035–2043, 2004), NMA was performed for a full-atom system using dihedral angles as independent variables, and we released the results (fluctuations of atoms, fluctuations of dihedral angles, correlations between atomic fluctuations, etc.). The vibrating oligomer is visualized by animation in an interactive molecular viewer for each of the 20 lowest-frequency normal modes. In addition, displacement vectors of constituent atoms for each normal mode were decomposed into two characteristic motions in individual subunits, i.e., internal and external (deformation and rigid-body movements of the individual subunits, respectively), and then the mutual movements of the subunits and the movement of atoms around the interface regions were investigated. These results released in ProMode-Oligomer are useful for characterizing oligomeric proteins from a dynamic point of view. The analyses are illustrated with immunoglobulin light- and heavy-chain variable domains bound to lysozyme and to a 12-residue peptide.
26
Connell, J. W., J. G. Smith, and P. M. Hergenrother. "Imide Oligomers Containing Pendent and Terminal Phenylethynyl Groups—II." High Performance Polymers 10, no. 3 (September 1998): 273–83. http://dx.doi.org/10.1088/0954-0083/10/3/005.
Full textAbstract:
As part of a programme to develop high-performance/high-temperature structural resins for aeronautical applications, imide oligomers containing pendent and terminal phenylethynyl groups were prepared, characterized and the cured resins evaluated as composite matrices. The oligomers were prepared at a calculated number-average molecular weight of 5000 g mol−1 and contained 15–20 mol% pendent phenylethynyl groups. In previous work, an oligomer containing pendent and terminal phenylethynyl groups exhibited a high glass transition temperature (∼313 °C), and laminates therefrom exhibited high compressive properties, but processability, fracture toughness, microcrack resistance and damage tolerance were less than desired. In an attempt to improve these deficiencies, modifications in the oligomeric backbone involving the incorporation of 1,3-bis(3-aminophenoxy)benzene were investigated as a means of improving processability and toughness without detracting from the high glass transition temperature and high compressive properties. The amide acid oligomeric solutions were prepared in N-methyl-2-pyrrolidinone and were subsequently processed into imide powder, thin films, adhesive tape and carbon fibre prepreg. Neat resin plaques were fabricated from imide powder by compression moulding. The maximum processing pressure was 1.4 MPa and the cure temperature ranged from 350 to 371 °C for 1 h for the mouldings, adhesives, films and composites. The properties of the 1,3-bis(3-aminophenoxy)benzene modified cured imide oligomers containing pendent and terminal phenylethynyl groups are compared with those of previously prepared oligomers containing pendent and terminal phenylethynyl groups of similar composition and molecular weight.
27
Orlov, Y. N. "The impact of the of cationic polyelectrolyte polymerization degree in latexes coagulation dosage of synthetic emulsion rubbers." Proceedings of the Voronezh State University of Engineering Technologies 81, no. 1 (July 18, 2019): 318–24. http://dx.doi.org/10.20914/2310-1202-2019-1-318-324.
Full textAbstract:
The literature data on the parameters of coagulation of butadiene-styrene and butadiene-?-methyl styrene latexes by cationic polyelectrolytes in comparison with low-molecular ammonium compounds and nonionic polymers are discussed. The optimal dosage of cationic polyelectrolyte during coagulation of synthetic emulsion rubber latex stabilized by a combination of synthetic fatty acid Soaps and disproportionated rosin with a mixture of sodium salts of the oligomeric condensation product ?-naphthalenesulfonic acid with formaldehyde (Leukanol) is determined, ceteris paribus, by its degree of polymerization. The decrease in the optimum dosage during the transition from high molecular weight polyelectrolytes to the oligomers caused by decrease of the cationic and anionic groups ratio required for a complete binding Leukanol in the formation of oligomer-oligomer complexes compared with the polymer-oligomer complexes. This is due, apparently, the fact that an increase in the average molecular weight of the polyelectrolyte increases the proportion of so-called tails and loops, consisting of units of the polyelectrolyte that are not associated with molecules Leukanol
28
Poon, G. M. K. "Enhancement of oligomeric stability by covalent linkage and its application to the human p53tet domain: thermodynamics and biological implications." Biochemical Society Transactions 35, no. 6 (November 23, 2007): 1574–78. http://dx.doi.org/10.1042/bst0351574.
Full textAbstract:
The formation of oligomeric proteins proceeds at a major cost of reducing the translational and rotational entropy for their subunits in order to form the stabilizing interactions found in the oligomeric state. Unlike site-directed mutations, covalent linkage of subunits represents a generically applicable strategy for enhancing oligomeric stability by reducing the entropic driving force for dissociation. Although this can be realized by introducing de novo disulfide cross-links between subunits, issues with irreversible aggregation limit the utility of this approach. In contrast, tandem linkage of subunits in a single polypeptide chain offers a universal method of pre-paying the entropic cost of oligomer formation. In the present paper, thermodynamic, structural and experimental aspects of designing and characterizing tandem-linked oligomers are discussed with reference to engineering a stabilized tetramer of the oligomerization domain of the human p53 tumour-suppressor protein by tandem dimerization.
29
Sanganna Gari, Raghavendar Reddy, Patrick Seelheim, Brendan Marsh, Volker Kiessling, Carl E. Creutz, and Lukas K. Tamm. "Quaternary structure of the small amino acid transporter OprG from Pseudomonas aeruginosa." Journal of Biological Chemistry 293, no. 44 (September 20, 2018): 17267–77. http://dx.doi.org/10.1074/jbc.ra118.004461.
Full textAbstract:
Pseudomonas aeruginosa is an opportunistic human pathogen that causes nosocomial infections. The P. aeruginosa outer membrane contains specific porins that enable substrate uptake, with the outer membrane protein OprG facilitating transport of small, uncharged amino acids. However, the pore size of an eight-stranded β-barrel monomer of OprG is too narrow to accommodate even the smallest transported amino acid, glycine, raising the question of how OprG facilitates amino acid uptake. Pro-92 of OprG is critically important for amino acid transport, with a P92A substitution inhibiting transport and the NMR structure of this variant revealing that this substitution produces structural changes in the barrel rim and restricts loop motions. OprG may assemble into oligomers in the outer membrane (OM) whose subunit interfaces could form a transport channel. Here, we explored the contributions of the oligomeric state and the extracellular loops to OprG's function. Using chemical cross-linking to determine the oligomeric structures of both WT and P92A OprG in native outer membranes and atomic force microscopy, and single-molecule fluorescence of the purified proteins reconstituted into lipid bilayers, we found that both protein variants form oligomers, supporting the notion that subunit interfaces in the oligomer could provide a pathway for amino acid transport. Furthermore, performing transport assays with loop-deleted OprG variants, we found that these variants also can transport small amino acids, indicating that the loops are not solely responsible for substrate transport. We propose that OprG functions as an oligomer and that conformational changes in the barrel–loop region might be crucial for its activity.
30
Puglisi, Roberta, Placido G. Mineo, Andrea Pappalardo, Antonino Gulino, and Giuseppe Trusso Sfrazzetto. "Supramolecular Detection of a Nerve Agent Simulant by Fluorescent Zn–Salen Oligomer Receptors." Molecules 24, no. 11 (June 8, 2019): 2160. http://dx.doi.org/10.3390/molecules24112160.
Full textAbstract:
We report on new Zn–Salen oligomer receptors able to recognize a nerve agent simulant, namely dimethyl methylphosphonate (DMMP), by a supramolecular approach. In particular, three Zn-Salen oligomers (Zn–Oligo–A, –B, and –C), differing by the length distribution, were obtained and characterized by NMR, Gel Permeation Chromatography (GPC), UV-Vis, and fluorescence spectroscopy. Furthermore, we investigated their recognition properties towards DMMP by using fluorescence measurements. We found that the recognition ability depends on the length of the oligomeric chain, and the Zn–Oligo–C shows a binding constant value higher than those already reported in literature for the DMMP detection.
31
Sokolov, Yuri, J. Ashot Kozak, Rakez Kayed, Alexandr Chanturiya, Charles Glabe, and James E. Hall. "Soluble Amyloid Oligomers Increase Bilayer Conductance by Altering Dielectric Structure." Journal of General Physiology 128, no. 6 (November 13, 2006): 637–47. http://dx.doi.org/10.1085/jgp.200609533.
Full textAbstract:
The amyloid hypothesis of Alzheimer's toxicity has undergone a resurgence with increasing evidence that it is not amyloid fibrils but a smaller oligomeric species that produces the deleterious results. In this paper we address the mechanism of this toxicity. Only oligomers increase the conductance of lipid bilayers and patch-clamped mammalian cells, producing almost identical current–voltage curves in both preparations. Oligomers increase the conductance of the bare bilayer, the cation conductance induced by nonactin, and the anion conductance induced by tetraphenyl borate. Negative charge reduces the sensitivity of the membrane to amyloid, but cholesterol has little effect. In contrast, the area compressibility of the lipid has a very large effect. Membranes with a large area compressibility modulus are almost insensitive to amyloid oligomers, but membranes formed from soft, highly compressible lipids are highly susceptible to amyloid oligomer-induced conductance changes. Furthermore, membranes formed using the solvent decane (instead of squalane) are completely insensitive to the presence of oligomers. One simple explanation for these effects on bilayer conductance is that amyloid oligomers increase the area per molecule of the membrane-forming lipids, thus thinning the membrane, lowering the dielectric barrier, and increasing the conductance of any mechanism sensitive to the dielectric barrier.
32
Lee, Young A., Eun Ju Cho, and Takako Yokozawa. "Oligomeric proanthocyanidins improve memory and enhance phosphorylation of vascular endothelial growth factor receptor-2 in senescence-accelerated mouse prone/8." British Journal of Nutrition 103, no. 4 (October 13, 2009): 479–89. http://dx.doi.org/10.1017/s0007114509992005.
Full textAbstract:
Senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence, shows age-related deficits in learning and memory. We investigated the effect of oligomeric proanthocyanidins (oligomers) on memory impairment using the SAMP8 model involving the oral administration of oligomers for 5 weeks. To analyse memory improvement in SAMP8, we performed Morris water maze, object location and object recognition tests. The oral administration of oligomers improved spatial and object recognition impairment in SAMP8. Expressions of phosphorylated neurofilament-H (P-NF-H, axon marker), microtubule-associated proteins (MAP) 2a and 2b (MAP2; dendrite marker) and synaptophysin were increased in the brains of SAMP8-administered oligomers. In particular, the expression of P-NF-H was significantly elevated in the hippocampal CA1. This indicates that oligomers result in an increase in the densities of axons, dendrites and synapses. To investigate the protective mechanisms of oligomers against brain dysfunction with ageing, we carried out a receptor tyrosine kinase phosphorylation antibody array, and clarified that the administration of oligomers led to an increase in the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2, suggesting the neuroprotective role of oligomers. The phosphorylation of VEGFR-2 was more greatly increased in the hypothalamus and choroid plexus than in other brain regions of SAMP8. Memory in oligomer-treated mice was impaired by SU1498, a VEGFR-2-specific antagonist. Elucidating the relationship between memory impairment with ageing and VEGFR-2 signalling may provide new suggestions for protection against memory deficit in the ageing brain.
33
Li, H., E. Burts, K. Bears, Q. Ji, J. J. Lesko, D. A. Dillard, J. S. Riffle, and P. M. Puckett. "Network Structure and Properties of Dimethacrylate-Styrene Matrix Materials." Journal of Composite Materials 34, no. 18 (September 2000): 1512–28. http://dx.doi.org/10.1106/q064-0u44-fwdj-9let.
Full textAbstract:
One of the major classes of polymer matrix resins under consideration for structural composite applications in the infrastructure and construction industries is theso-called "vinyl esters." These are comprised of low molecular weight poly (hydroxyether) oligomers with methacrylate endgroups diluted with styrene monomer. The methacrylate oligomeric endgroups co-cure with the styrene in free radical copolymerization to yield thermoset networks. Selected properties of such resins and resultant networks where the molecular weights of the poly(hydroxyether) oligomers have been varied from 700 to 1200 g/mole and the concentration of styrene has been systematically changed are presented. In general, both the glass transition temperatures and fracture toughness of the fully cured networks increased as the styrene was decreased in each oligomer series with different molecular weights. As expected, the volume contraction upon cure also decreased significantly as styrene was decreased, and thus residual cure stresses may be reduced in fiber reinforced composites. The resistance to crack propagation was significantly improved for networks prepared with the 1200 M n dimethacrylate oligomer relative to those from the 700 g/mole material. Crosslink densities were estimated from measurements of the rubbery moduli at T g + 40°C and relationships between network density, chemical composition and properties are discussed.
34
Rodigast, Maria, Anke Mutzel, and Hartmut Herrmann. "A quantification method for heat-decomposable methylglyoxal oligomers and its application on 1,3,5-trimethylbenzene SOA." Atmospheric Chemistry and Physics 17, no. 6 (March 23, 2017): 3929–43. http://dx.doi.org/10.5194/acp-17-3929-2017.
Full textAbstract:
Abstract. Methylglyoxal forms oligomeric compounds in the atmospheric aqueous particle phase, which could establish a significant contribution to the formation of aqueous secondary organic aerosol (aqSOA). Thus far, no suitable method for the quantification of methylglyoxal oligomers is available despite the great effort spent for structure elucidation. In the present study a simplified method was developed to quantify heat-decomposable methylglyoxal oligomers as a sum parameter. The method is based on the thermal decomposition of oligomers into methylglyoxal monomers. Formed methylglyoxal monomers were detected using PFBHA (o-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride) derivatisation and gas chromatography–mass spectrometry (GC/MS) analysis. The method development was focused on the heating time (varied between 15 and 48 h), pH during the heating process (pH = 1–7), and heating temperature (50, 100 °C). The optimised values of these method parameters are presented. The developed method was applied to quantify heat-decomposable methylglyoxal oligomers formed during the OH-radical oxidation of 1,3,5-trimethylbenzene (TMB) in the Leipzig aerosol chamber (LEipziger AerosolKammer, LEAK). Oligomer formation was investigated as a function of seed particle acidity and relative humidity. A fraction of heat-decomposable methylglyoxal oligomers of up to 8 % in the produced organic particle mass was found, highlighting the importance of those oligomers formed solely by methylglyoxal for SOA formation. Overall, the present study provides a new and suitable method for quantification of heat-decomposable methylglyoxal oligomers in the aqueous particle phase.
35
Decraene, L. P. Ronse, and E. Smets. "The distribution and the systematic relevance of the androecial characters oligomery and polymery in the Magnoliophytina." Nordic Journal of Botany 7, no. 3 (June 1987): 239–53. http://dx.doi.org/10.1111/j.1756-1051.1987.tb00936.x.
Full text
36
LIBONATI, Massimo, and Giovanni GOTTE. "Oligomerization of bovine ribonuclease A: structural and functional features of its multimers." Biochemical Journal 380, no. 2 (June 1, 2004): 311–27. http://dx.doi.org/10.1042/bj20031922.
Full textAbstract:
Bovine pancreatic RNase A (ribonuclease A) aggregates to form various types of catalytically active oligomers during lyophilization from aqueous acetic acid solutions. Each oligomeric species is present in at least two conformational isomers. The structures of two dimers and one of the two trimers have been solved, while plausible models have been proposed for the structures of a second trimer and two tetrameric conformers. In this review, these structures, as well as the general conditions for RNase A oligomerization, based on the well known 3D (three-dimensional) domain-swapping mechanism, are described and discussed. Attention is also focused on some functional properties of the RNase A oligomers. Their enzymic activities, particularly their ability to degrade double-stranded RNAs and polyadenylate, are summarized and discussed. The same is true for the remarkable antitumour activity of the oligomers, displayed in vitro and in vivo, in contrast with monomeric RNase A, which lacks these activities. The RNase A multimers also show an aspermatogenic action, but lack any detectable embryotoxicity. The fact that both activity against double-stranded RNA and the antitumour action increase with the size of the oligomer suggests that these activities may share a common structural requirement, such as a high number or density of positive charges present on the RNase A oligomers.
37
NEMOTO, Takayuki, and Nobuko SATO. "Oligomeric forms of the 90-kDa heat shock protein." Biochemical Journal 330, no. 2 (March 1, 1998): 989–95. http://dx.doi.org/10.1042/bj3300989.
Full textAbstract:
Two isoforms of the 90-kDa heat shock protein, HSP90α and HSP90β, are present in the cytosol of mammalian cells. Analysis by polyacrylamide gel electrophoresis under nondenaturing conditions (native PAGE) revealed that HSP90α predominantly exists as a homodimer and that HSP90β is present mainly as a monomer [Minami, Kawasaki, Miyata, Suzuki and Yahara (1991) J. Biol. Chem. 266, 10099-10103]. However, only the dimeric form has been observed under other analytical conditions such as gradient centrifugation. In this study, therefore, we investigated native forms of HSP90 by use of immunochemical techniques with isoform-specific monoclonal antibodies recently developed in our laboratory. Glycerol gradient centrifugation at the physiological salt concentration as well as native PAGE analysis of rat liver cytosol revealed oligomeric forms of HSP90α sedimenting at 8-10S as predominant ones. On the other hand, the glycerol gradient centrifugation revealed multiple forms of HSP90β oligomers sedimenting at 6-12S. All of the HSP90β oligomers, however, migrated at 100-kDa monomer and 190-kDa dimer positions on native PAGE. A novel two-dimensional double native PAGE revealed that the entity was converted from the HSP90β dimer to monomers during the electrophoresis. The same PAGE further revealed that the HSP90α oligomer also dissociated into dimers during the electrophoresis. Full-length form of bacterially-expressed human HSP90α migrated as dimers, but a considerable amount did not penetrate into the gel under native PAGE conditions, indicating the existence of oligomeric forms. Electrophoretic studies of deletion mutants of HSP90 demonstrated that the C-terminal 200 amino acids were capable of forming oligomers. Taken together, we conclude that both of the HSP90 isoforms predominantly exist as oligomeric forms in the cytosol even under unstressed conditions but that they artificially dissociate into smaller forms when subjected to native PAGE.
38
Tian, Huilai, Eliot Davidowitz, Patricia Lopez, Sharareh Emadi, James Moe, and Michael Sierks. "Trimeric Tau Is Toxic to Human Neuronal Cells at Low Nanomolar Concentrations." International Journal of Cell Biology 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/260787.
Full textAbstract:
In Alzheimer’s disease (AD), tau aggregates into fibrils and higher order neurofibrillary tangles, a key histopathological feature of AD. However, soluble oligomeric tau species may play a more critical role in AD progression since these tau species correlate better with neuronal loss and cognitive dysfunction. Recent studies show that extracellular oligomeric tau can inhibit memory formation and synaptic function and also transmit pathology to neighboring neurons. However, the specific forms of oligomeric tau involved in toxicity are still unknown. Here, we used two splice variants of recombinant human tau and generated monomeric, dimeric, and trimeric fractions of each isoform. The composition of each fraction was verified chromatographically and also by atomic force microscopy. The toxicity of each fraction toward both human neuroblastoma cells and cholinergic-like neurons was assessed. Trimeric, but not monomeric or dimeric, tau oligomers of both splice variants were neurotoxic at low nanomolar concentrations. Further characterization of tau oligomer species with disease-specific modifications and morphologies is necessary to identify the best targets for the development of biomarker and therapeutic development for AD and related tauopathies.
39
Markina, Anastasia, Alexander Muratov, Vladislav Petrovskyy, and Vladik Avetisov. "Detection of Single Molecules Using Stochastic Resonance of Bistable Oligomers." Nanomaterials 10, no. 12 (December 15, 2020): 2519. http://dx.doi.org/10.3390/nano10122519.
Full textAbstract:
Ultra-sensitive elements for nanoscale devices capable of detecting single molecules are in demand for many important applications. It is generally accepted that the inevitable stochastic disturbance of a sensing element by its surroundings will limit detection at the molecular level. However, a phenomenon exists (stochastic resonance) in which the environmental noise acts abnormally: it amplifies, rather than distorts, a weak signal. Stochastic resonance is inherent in non-linear bistable systems with criticality at which the bistability emerges. Our computer simulations have shown that the large-scale conformational dynamics of a short oligomeric fragment of thermosrespective polymer, poly-N-isopropylmethacrylamid, resemble the mechanical movement of nonlinear bistable systems. The oligomers we have studied demonstrate spontaneous vibrations and stochastic resonance activated by conventional thermal noise. We have observed reasonable shifts of the spontaneous vibrations and stochastic resonance modes when attaching an analyte molecule to the oligomer. Our simulations have shown that spontaneous vibrations and stochastic resonance of the bistable thermoresponsive oligomers are sensitive to both the analyte molecular mass and the binding affinity. All these effects indicate that the oligomers with mechanic-like bistability may be utilized as ultrasensitive operational units capable of detecting single molecules.
40
Tanner, John J. "Empirical power laws for the radii of gyration of protein oligomers." Acta Crystallographica Section D Structural Biology 72, no. 10 (September 15, 2016): 1119–29. http://dx.doi.org/10.1107/s2059798316013218.
Full textAbstract:
The radius of gyration is a fundamental structural parameter that is particularly useful for describing polymers. It has been known since Flory's seminal work in the mid-20th century that polymers show a power-law dependence, where the radius of gyration is proportional to the number of residues raised to a power. The power-law exponent has been measured experimentally for denatured proteins and derived empirically for folded monomeric proteins using crystal structures. Here, the biological assemblies in the Protein Data Bank are surveyed to derive the power-law parameters for protein oligomers having degrees of oligomerization of 2–6 and 8. The power-law exponents for oligomers span a narrow range of 0.38–0.41, which is close to the value of 0.40 obtained for monomers. This result shows that protein oligomers exhibit essentially the same power-law behavior as monomers. A simple power-law formula is provided for estimating the oligomeric state from an experimental measurement of the radius of gyration. Several proteins in the Protein Data Bank are found to deviate substantially from power-law behavior by having an atypically large radius of gyration. Some of the outliers have highly elongated structures, such as coiled coils. For coiled coils, the radius of gyration does not follow a power law and instead scales linearly with the number of residues in the oligomer. Other outliers are proteins whose oligomeric state or quaternary structure is incorrectly annotated in the Protein Data Bank. The power laws could be used to identify such errors and help prevent them in future depositions.
41
Müller, L., M. C. Reinnig, J. Warnke, and Th Hoffmann. "Unambiguous identification of esters as oligomers in secondary organic aerosol formed from cyclohexene and cyclohexene/α-pinene ozonolysis." Atmospheric Chemistry and Physics 8, no. 5 (March 11, 2008): 1423–33. http://dx.doi.org/10.5194/acp-8-1423-2008.
Full textAbstract:
Abstract. The build-up of oligomeric compounds during secondary organic aerosol (SOA) formation is subject of atmospheric research since several years. New particle formation and especially the SOA mass yield might be influenced significantly by oligomer formation. However, the chemical nature of observed oligomers and their formation pathways are still unclear. In this paper, the structural characterization of certain dimeric compounds (esters) formed during the ozonolysis of cyclohexene and cyclohexene/α-pinene mixtures are presented. The identification is based on the comparison of the mass spectra and the retention times (LC) of the oligomeric products with synthesized reference compounds. Cyclohexene is used here as a model compound for terpenes as globally most important SOA precursors, since it possesses a simpler structure than the biogenic alkenes and therefore offers the possibility to get access to reference compounds for certain of its oxidation products. In addition to cyclohexene, the formation of esters could also be observed in experiments with α-pinene as reactant.
42
Müller, L., M. C. Reinnig, J. Warnke, and T. Hoffmann. "Unambiguous identification of esters as oligomers in secondary organic aerosol formed from cyclohexene and cyclohexene/α-pinene ozonolysis." Atmospheric Chemistry and Physics Discussions 7, no. 5 (September 26, 2007): 13883–913. http://dx.doi.org/10.5194/acpd-7-13883-2007.
Full textAbstract:
Abstract. The built-up of oligomeric compounds during secondary organic aerosol (SOA) formation is subject of atmospheric research since several years. New particle formation and especially the SOA mass yield might be influenced significantly by oligomer formation. However, the chemical nature of observed oligomers and their formation pathways are still unclear. In this paper, the structural characterization of certain dimeric compounds (esters) formed during the ozonolysis of cyclohexene and cyclohexene/α-pinene mixtures are presented. The identification is based on the comparison of the mass spectra and the retention times (LC) of the oligomeric products with synthesized reference compounds. Cyclohexene is used here as a model compound for terpenes as globally most important SOA precursors, since it possesses a simpler structure than the biogenic alkenes and therefore offers the possibility to get access to reference compounds for certain of its oxidation products. In addition to cyclohexene, the formation of esters could also be observed in experiments with α-pinene as reactant.
43
Iljina, Marija, Gonzalo A. Garcia, Mathew H. Horrocks, Laura Tosatto, Minee L. Choi, Kristina A. Ganzinger, Andrey Y. Abramov, et al. "Kinetic model of the aggregation of alpha-synuclein provides insights into prion-like spreading." Proceedings of the National Academy of Sciences 113, no. 9 (February 16, 2016): E1206—E1215. http://dx.doi.org/10.1073/pnas.1524128113.
Full textAbstract:
The protein alpha-synuclein (αS) self-assembles into small oligomeric species and subsequently into amyloid fibrils that accumulate and proliferate during the development of Parkinson’s disease. However, the quantitative characterization of the aggregation and spreading of αS remains challenging to achieve. Previously, we identified a conformational conversion step leading from the initially formed oligomers to more compact oligomers preceding fibril formation. Here, by a combination of single-molecule fluorescence measurements and kinetic analysis, we find that the reaction in solution involves two unimolecular structural conversion steps, from the disordered to more compact oligomers and then to fibrils, which can elongate by further monomer addition. We have obtained individual rate constants for these key microscopic steps by applying a global kinetic analysis to both the decrease in the concentration of monomeric protein molecules and the increase in oligomer concentrations over a 0.5–140-µM range of αS. The resulting explicit kinetic model of αS aggregation has been used to quantitatively explore seeding the reaction by either the compact oligomers or fibrils. Our predictions reveal that, although fibrils are more effective at seeding than oligomers, very high numbers of seeds of either type, of the order of 104, are required to achieve efficient seeding and bypass the slow generation of aggregates through primary nucleation. Complementary cellular experiments demonstrated that two orders of magnitude lower numbers of oligomers were sufficient to generate high levels of reactive oxygen species, suggesting that effective templated seeding is likely to require both the presence of template aggregates and conditions of cellular stress.
44
Xiao, Yiling, Isamu Matsuda, Masafumi Inoue, Tomoya Sasahara, Minako Hoshi, and Yoshitaka Ishii. "NMR-based site-resolved profiling of β-amyloid misfolding reveals structural transitions from pathologically relevant spherical oligomer to fibril." Journal of Biological Chemistry 295, no. 2 (November 26, 2019): 458–67. http://dx.doi.org/10.1074/jbc.ra119.008522.
Full textAbstract:
Increasing evidence highlights the central role of neurotoxic oligomers of the 42-residue-long β-amyloid (Aβ42) in Alzheimer's disease (AD). However, very limited information is available on the structural transition from oligomer to fibril, particularly for pathologically relevant amyloids. To the best of our knowledge, we present here the first site-specific structural characterization of Aβ42 misfolding, from toxic oligomeric assembly yielding a similar conformation to an AD-associated Aβ42 oligomer, into a fibril. Transmission EM (TEM) analysis revealed that a spherical amyloid assembly (SPA) of Aβ42 with a 15.6 ± 2.1-nm diameter forms in a ∼30-μm Aβ42 solution after a ∼10-h incubation at 4 °C, followed by a slow conversion into fibril at ∼180 h. Immunological analysis suggested that the SPA has a surface structure similar to that of amylospheroid (ASPD), a patient-derived toxic Aβ oligomer, which had a diameter of 10–15 nm in negative-stain TEM. Solid-state NMR analyses indicated that the SPA structure involves a β-loop-β motif, which significantly differed from the triple-β motif observed for the Aβ42 fibril. The comparison of the 13C chemical shifts of SPA with those of the fibril prepared in the above conditions and interstrand distance measurements suggested a large conformational change involving rearrangements of intermolecular β-sheet into in-register parallel β-sheet during the misfolding. A comparison of the SPA and ASPD 13C chemical shifts indicated that SPA is structurally similar to the ASPD relevant to AD. These observations provide insights into the architecture and key structural transitions of amyloid oligomers relevant for AD pathology.
45
Kim, Hyo Geun, Ji-Young Kim, Wei-Wan Whang, and Myung Sook Oh. "Neuroprotective effect of Chunghyuldan from amyloid beta oligomer induced neuroinflammation in vitro and in vivo." Canadian Journal of Physiology and Pharmacology 92, no. 6 (June 2014): 429–37. http://dx.doi.org/10.1139/cjpp-2013-0229.
Full textAbstract:
Microglia-mediated inflammation is a major pathological mechanism contributing to Alzheimer’s disease (AD), and has been proposed as a potential therapeutic target. Chunghyuldan (CHD; Qingxue-dan in Chinese and Daio-Orengedokuto in Japanese) possesses wide-ranging biological effects, including anti-hyperlipidemic, anti-stroke, anti-inflammatory, and antioxidant activities that could affect neurological functions. In this study, we examined the effects of CHD in in-vitro and in-vivo models of AD induced by the oligomeric form of amyloid-beta (Aβ oligomer), which acts directly on microglia-mediated neuroinflammation to result in neuronal damage and cognitive impairment. CHD at 0.1–100 μg·mL−1 significantly protected PC12 cells and rat primary hippocampal cells from Aβ oligomer1–42 toxicity. In addition, CHD at 1–10 μg·mL−1 inhibited Aβ oligomer1–42 induced production of nitric oxide, tumor necrosis factor-α, and interleukin-1β in microglial cells. In an in-vivo AD model, administration of CHD (50 mg·(kg body mass)−1, for 5 days, per oral) inhibited the activation of astrocytes and microglia in the dentate gyrus and neuronal damage in the CA1 of the ipsilateral hippocampus. Moreover, CHD ameliorated cognitive impairment induced by Aβ oligomer1–42 toxicity. These results demonstrate the neuroprotective effects of CHD through inhibition of microglia-mediated neuroinflammation in in-vitro and in-vivo AD-like models induced by Aβ oligomer1–42 toxicity.
46
Celej, María Soledad, Rabia Sarroukh, Erik Goormaghtigh, Gerardo D. Fidelio, Jean-Marie Ruysschaert, and Vincent Raussens. "Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure." Biochemical Journal 443, no. 3 (April 16, 2012): 719–26. http://dx.doi.org/10.1042/bj20111924.
Full textAbstract:
Parkinson's disease is an age-related movement disorder characterized by the presence in the mid-brain of amyloid deposits of the 140-amino-acid protein AS (α-synuclein). AS fibrillation follows a nucleation polymerization pathway involving diverse transient prefibrillar species varying in size and morphology. Similar to other neurodegenerative diseases, cytotoxicity is currently attributed to these prefibrillar species rather than to the insoluble aggregates. Nevertheless, the underlying molecular mechanisms responsible for cytotoxicity remain elusive and structural studies may contribute to the understanding of both the amyloid aggregation mechanism and oligomer-induced toxicity. It is already recognized that soluble oligomeric AS species adopt β-sheet structures that differ from those characterizing the fibrillar structure. In the present study we used ATR (attenuated total reflection)–FTIR (Fourier-transform infrared) spectroscopy, a technique especially sensitive to β-sheet structure, to get a deeper insight into the β-sheet organization within oligomers and fibrils. Careful spectral analysis revealed that AS oligomers adopt an antiparallel β-sheet structure, whereas fibrils adopt a parallel arrangement. The results are discussed in terms of regions of the protein involved in the early β-sheet interactions and the implications of such conformational arrangement for the pathogenicity associated with AS oligomers.
47
Pokrajac, Lisa, Clara Baik, J. Robin Harris, Naghmeh S. Sarraf, and Michael Palmer. "Partial oligomerization of pyolysin induced by a disulfide-tethered mutant." Biochemistry and Cell Biology 90, no. 6 (December 2012): 709–17. http://dx.doi.org/10.1139/o2012-029.
Full textAbstract:
The bacterial toxin pyolysin (PLO) belongs to the family of cholesterol-dependent cytolysins (CDCs), which form large, ring-shaped oligomeric pores in cholesterol-containing membranes. Monomeric CDC molecules have a structure of four domains, with domains 2 and 3 packed against each other. After binding to target membranes containing cholesterol, toxin monomers oligomerize into pre-pore complexes. Trans-membrane pores form when the pre-pores insert into the lipid bilayer. Membrane insertion requires each subunit in the pre-pore to undergo a significant change in conformation, including the separation of domains 2 and 3. We here characterize a pyolysin mutant with an engineered disulfide bond between domains 2 and 3. The disulfide-tethered mutant binds to membranes but does not form oligomers. When mixed with wild type PLO, the two proteins form hybrid oligomers, which are reduced in size and arc-shaped rather than ring-shaped. With equimolar mixtures or the disulfide mutant in slight excess, the hybrid oligomers retain pore-forming activity, while a larger excess of the mutant suppresses pore formation. These results support a “partially cooperative” mode of protein activity, in which a limited number of functional subunits within an oligomer have to cooperate to initiate membrane insertion and pore formation.
48
Demuro, Angelo, Martin Smith, and Ian Parker. "Single-channel Ca2+ imaging implicates Aβ1–42 amyloid pores in Alzheimer’s disease pathology." Journal of Cell Biology 195, no. 3 (October 24, 2011): 515–24. http://dx.doi.org/10.1083/jcb.201104133.
Full textAbstract:
Oligomeric forms of Aβ peptides are implicated in Alzheimer’s disease (AD) and disrupt membrane integrity, leading to cytosolic calcium (Ca2+) elevation. Proposed mechanisms by which Aβ mediates its effects include lipid destabilization, activation of native membrane channels, and aggregation of Aβ into Ca2+-permeable pores. We distinguished between these using total internal reflection fluorescence (TIRF) microscopy to image Ca2+ influx in Xenopus laevis oocytes. Aβ1–42 oligomers evoked single-channel Ca2+ fluorescence transients (SCCaFTs), which resembled those from classical ion channels but which were not attributable to endogenous oocyte channels. SCCaFTs displayed widely variable open probabilities (Po) and stepwise transitions among multiple amplitude levels reminiscent of subconductance levels of ion channels. The proportion of high Po, large amplitude SCCaFTs grew with time, suggesting that continued oligomer aggregation results in the formation of highly toxic pores. We conclude that formation of intrinsic Ca2+-permeable membrane pores is a major pathological mechanism in AD and introduce TIRF imaging for massively parallel single-channel studies of the incorporation, assembly, and properties of amyloidogenic oligomers.
49
Rowan, M. J., I. Klyubin, Q. Wang, N. W. Hu, and R. Anwyl. "Synaptic memory mechanisms: Alzheimer's disease amyloid β-peptide-induced dysfunction." Biochemical Society Transactions 35, no. 5 (October 25, 2007): 1219–23. http://dx.doi.org/10.1042/bst0351219.
Full textAbstract:
There is growing evidence that mild cognitive impairment in early AD (Alzheimer's disease) may be due to synaptic dysfunction caused by the accumulation of non-fibrillar, oligomeric Aβ (amyloid β-peptide), long before widespread synaptic loss and neurodegeneration occurs. Soluble Aβ oligomers can rapidly disrupt synaptic memory mechanisms at extremely low concentrations via stress-activated kinases and oxidative/nitrosative stress mediators. Here, we summarize experiments that investigated whether certain putative receptors for Aβ, the αv integrin extracellular cell matrix-binding protein and the cytokine TNFα (tumour necrosis factor α) type-1 death receptor mediate Aβ oligomer-induced inhibition of LTP (long-term potentiation). Ligands that neutralize TNFα or genetic knockout of TNF-R1s (type-1 TNFα receptors) prevented Aβ-triggered inhibition of LTP in hippocampal slices. Similarly, antibodies to αv-containing integrins abrogated LTP block by Aβ. Protection against the synaptic plasticity-disruptive effects of soluble Aβ was also achieved using systemically administered small molecules targeting these mechanisms in vivo. Taken together, this research lends support to therapeutic trials of drugs antagonizing synaptic plasticity-disrupting actions of Aβ oligomers in preclinical AD.
50
BÖDE, Csaba, Ferenc G. TÖLGYESI, László SMELLER, Karel HEREMANS, Sergiy V. AVILOV, and Judit FIDY. "Chaperone-like activity of alpha-crystallin is enhanced by high-pressure treatment." Biochemical Journal 370, no. 3 (March 15, 2003): 859–66. http://dx.doi.org/10.1042/bj20021097.
Full textAbstract:
α-Crystallin, an oligomeric protein in vertebrate eye lens, is a member of the small heat-shock protein family. Several papers pointed out that its chaperone-like activity could be enhanced by increasing the temperature. We demonstrate in the present study that structural perturbations by high hydrostatic pressures up to 300MPa also enhance this activity. In contrast with temperature-induced changes, the pressure-induced enhancement is reversible. After pressure release, the extra activity is lost with a relaxation time of 2.0±0.5h. Structural alterations contributing to the higher activity were studied with IR and fluorescence spectroscopy, and light-scattering measurements. The results suggest that while the secondary structure barely changes under pressure, the interactions between the subunits weaken, the oligomers dissociate, the area of accessible hydrophobic surfaces significantly increases and the environment of tryptophan residues becomes slightly more polar. It seems that structural flexibility and the total surface area of the oligomers are the key factors in the chaperone capacity, and that the increase in the chaperone activity does not require the increase in the oligomer size as was assumed previously [Burgio, Kim, Dow and Koretz (2000) Biochem. Biophys. Res. Commun. 268, 426—432]. After pressure release, the structure of subunits are reorganized relatively quickly, whereas the oligomer size reaches its original value slowly with a relaxation time of 33±4 h. In our interpretation, both the fast and slow structural rearrangements have an impact on the functional relaxation.