A relationship between the transient structure in the monomeric state and the aggregation propensities of α-synuclein and β-synuclein.

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dc.contributor.author Allison, Jane R
dc.contributor.author Rivers, Robert C
dc.contributor.author Christodoulou, John C
dc.contributor.author Vendruscolo, Michele
dc.contributor.author Dobson, Christopher M
dc.coverage.spatial United States
dc.date.accessioned 2022-05-25T21:14:21Z
dc.date.available 2022-05-25T21:14:21Z
dc.date.issued 2014-11-12
dc.identifier.citation (2014). Biochemistry, 53(46), 7170-7183.
dc.identifier.issn 0006-2960
dc.identifier.uri https://hdl.handle.net/2292/59501
dc.description.abstract α-Synuclein is an intrinsically disordered protein whose aggregation is implicated in Parkinson's disease. A second member of the synuclein family, β-synuclein, shares significant sequence similarity with α-synuclein but is much more resistant to aggregation. β-Synuclein is missing an 11-residue stretch in the central non-β-amyloid component region that forms the core of α-synuclein amyloid fibrils, yet insertion of these residues into β-synuclein to produce the βSHC construct does not markedly increase the aggregation propensity. To investigate the structural basis of these different behaviors, quantitative nuclear magnetic resonance data, in the form of paramagnetic relaxation enhancement-derived interatomic distances, are combined with molecular dynamics simulations to generate ensembles of structures representative of the solution states of α-synuclein, β-synuclein, and βSHC. Comparison of these ensembles reveals that the differing aggregation propensities of α-synuclein and β-synuclein are associated with differences in the degree of residual structure in the C-terminus coupled to the shorter separation between the N- and C-termini in β-synuclein and βSHC, making protective intramolecular contacts more likely.
dc.format.medium Print-Electronic
dc.language eng
dc.publisher American Chemical Society (ACS)
dc.relation.ispartofseries Biochemistry
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
dc.subject Humans
dc.subject Parkinson Disease
dc.subject Sequence Alignment
dc.subject Amino Acid Sequence
dc.subject Protein Structure, Secondary
dc.subject Molecular Sequence Data
dc.subject alpha-Synuclein
dc.subject beta-Synuclein
dc.subject Molecular Dynamics Simulation
dc.subject Protein Aggregates
dc.subject Protein Aggregation, Pathological
dc.subject Neurosciences
dc.subject Neurodegenerative
dc.subject Acquired Cognitive Impairment
dc.subject Dementia
dc.subject Brain Disorders
dc.subject Parkinson's Disease
dc.subject 2.1 Biological and endogenous factors
dc.subject Neurological
dc.subject Science & Technology
dc.subject Life Sciences & Biomedicine
dc.subject Biochemistry & Molecular Biology
dc.subject INTRINSICALLY DISORDERED PROTEINS
dc.subject NUCLEAR-MAGNETIC-RESONANCE
dc.subject MOLECULAR-DYNAMICS SIMULATIONS
dc.subject RESIDUAL DIPOLAR COUPLINGS
dc.subject PARTIALLY FOLDED PROTEINS
dc.subject LONG-RANGE STRUCTURE
dc.subject DENATURED STATE
dc.subject PARAMAGNETIC RELAXATION
dc.subject DISTANCE RESTRAINTS
dc.subject CONFORMATIONAL PROPERTIES
dc.subject 0303 Macromolecular and Materials Chemistry
dc.subject 0304 Medicinal and Biomolecular Chemistry
dc.subject 0601 Biochemistry and Cell Biology
dc.subject 1101 Medical Biochemistry and Metabolomics
dc.title A relationship between the transient structure in the monomeric state and the aggregation propensities of α-synuclein and β-synuclein.
dc.type Journal Article
dc.identifier.doi 10.1021/bi5009326
pubs.issue 46
pubs.begin-page 7170
pubs.volume 53
dc.date.updated 2022-04-28T03:17:16Z
dc.rights.holder Copyright: The author en
dc.identifier.pmid 25389903 (pubmed)
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/25389903
pubs.end-page 7183
pubs.publication-status Published
dc.rights.accessrights http://purl.org/eprint/accessRights/RetrictedAccess en
pubs.subtype Research Support, Non-U.S. Gov't
pubs.subtype research-article
pubs.subtype Journal Article
pubs.elements-id 739583
pubs.org-id Science
pubs.org-id Biological Sciences
dc.identifier.eissn 1520-4995
pubs.record-created-at-source-date 2022-04-28
pubs.online-publication-date 2014-11-12


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