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Beta‐barrel models of soluble amyloid beta oligomers and annular protofibrils
Author(s) -
Shafrir Yi,
Durell Stewart R.,
Anishkin Andriy,
Guy H. Robert
Publication year - 2010
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22832
Subject(s) - barrel (horology) , chemistry , biophysics , fibril , molecular dynamics , amyloid fibril , protein structure , peptide , amyloid (mycology) , crystallography , biochemistry , amyloid β , biology , materials science , computational chemistry , medicine , inorganic chemistry , disease , pathology , composite material
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.