Auer, S., Meersman, F., Dobson, C.M. et al. (2 more authors) (2008) A Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric Aggregates. PLoS Computational Biology, 4 (11). e1000222. ISSN 1553-7358
Abstract
The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention because it has been associated with a range of neurodegenerative conditions including Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate that the formation of ordered arrays of hydrogen bonds drives the formation of β-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Individual β-sheets initially form with random orientations and subsequently tend to align into protofilaments as their lengths increase. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first-order phase transitions by showing that ordered cross-β structures emerge preferentially from disordered compact dynamical intermediate assemblies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2008 Auer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > University of Leeds Research Centres and Institutes > Centre for Self-Organising Molecular Systems (Leeds) |
Depositing User: | Sherpa Assistant |
Date Deposited: | 06 Nov 2009 15:02 |
Last Modified: | 04 Nov 2016 04:02 |
Published Version: | http://dx.doi.org/10.1371/journal.pcbi.1000222 |
Status: | Published |
Publisher: | Public Library of Science |
Identification Number: | doi: 10.1371/journal.pcbi.1000222 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:10096 |