Document Detail


Size distribution of amyloid nanofibrils.
MedLine Citation:
PMID:  22067163     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We consider the size distribution of amyloid nanofibrils (protofilaments) in nucleating protein solutions when the nucleation process occurs by the mechanism of direct polymerization of β-strands (extended peptides or protein segments) into β-sheets. Employing the atomistic nucleation theory, we derive a general expression for the stationary size distribution of amyloid nanofibrils constituted of successively layered β-sheets. The application of this expression to amyloid β(1-40) (Aβ(40)) fibrils allows us to determine the nanofibril size distribution as a function of the protein concentration and temperature. The distribution is most remarkable with its exhibiting a series of peaks positioned at "magic" nanofibril sizes (or lengths), which are due to deep local minima in the work for fibril formation. This finding of magic sizes or lengths is consistent with experimental results for the size distribution of aggregates in solutions of Aβ(40) proteins. Also, our approach makes it possible to gain insight into the effect of point mutations on the nanofibril size distribution, an effect that may play a role in experimentally observed substantial differences in the fibrillation lag-time of wild-type and point-mutated amyloid-β proteins.
Authors:
Raffaela Cabriolu; Dimo Kashchiev; Stefan Auer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-01
Journal Detail:
Title:  Biophysical journal     Volume:  101     ISSN:  1542-0086     ISO Abbreviation:  Biophys. J.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-09     Completed Date:  2012-02-29     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2232-41     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Affiliation:
Centre for Molecular Nanoscience, School of Chemistry, University of Leeds, Leeds, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Amyloid / chemistry*
Amyloid beta-Peptides / chemistry,  genetics
Nanofibers / chemistry*
Particle Size*
Point Mutation / genetics
Protein Structure, Secondary
Solubility
Thermodynamics
Chemical
Reg. No./Substance:
0/Amyloid; 0/Amyloid beta-Peptides
Comments/Corrections

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