This article is a US government work and, as such, is in the public domain in the United States of America.
Beta-barrel models of soluble amyloid beta oligomers and annular protofibrils†
Article first published online: 8 NOV 2010
Copyright © 2010 Wiley-Liss, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 78, Issue 16, pages 3458–3472, December 2010
How to Cite
Shafrir, Y., Durell, S. R., Anishkin, A. and Guy, H. R. (2010), Beta-barrel models of soluble amyloid beta oligomers and annular protofibrils. Proteins, 78: 3458–3472. doi: 10.1002/prot.22832
- Issue published online: 8 NOV 2010
- Article first published online: 8 NOV 2010
- Manuscript Accepted: 15 JUN 2010
- Manuscript Revised: 14 MAY 2010
- Manuscript Received: 18 FEB 2010
- Intramural Research Program of the NIH
- National Cancer Institute
- Center for Cancer Research
- molecular models;
- structure prediction;
- Alzheimer's disease;
- protein structure;
- molecular dynamics;
- molecular assemblies
Both soluble and membrane-bound prefibrillar assemblies of Abeta (Aβ) peptides have been associated with Alzheimer's disease (AD). The size and nature of these assemblies vary greatly and are affected by many factors. Here, we present models of soluble hexameric assemblies of Aβ42 and suggest how they can lead to larger assemblies and eventually to fibrils. The common element in most of these assemblies is a six-stranded β-barrel formed by the last third of Aβ42, which is composed of hydrophobic residues and glycines. The hydrophobic core β-barrels of the hexameric models are shielded from water by the N-terminus and central segments. These more hydrophilic segments were modeled to have either predominantly β or predominantly α secondary structure. Molecular dynamics simulations were performed to analyze stabilities of the models. The hexameric models were used as starting points from which larger soluble assemblies of 12 and 36 subunits were modeled. These models were developed to be consistent with numerous experimental results. Proteins 2010. © 2010 Wiley-Liss, Inc.