Beta-barrel models of soluble amyloid beta oligomers and annular protofibrils.

ABSTRACT: 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 perfo

SUBMITTER: Shafrir Y 

PROVIDER: S-EPMC2976788 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature