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Structure of ring-shaped A??? oligomers determined by conformational selection.

ABSTRACT: The oligomerization of amyloid beta (A?) peptides into soluble non-fibrillar species plays a critical role in the pathogenesis of Alzheimer's disease. However, it has been challenging to characterize the tertiary and quaternary structures of A? peptides due to their disordered nature and high aggregation propensity. In this work, replica exchange molecular dynamics simulations were used to explore the conformational space of A?42 monomer. Among the most populated transient states, we identified a particular conformation which was able to generate ring-shaped pentamers and hexamers, when docked onto itself. The structures of these aggregates were stable during microsecond all-atom MD simulations in explicit solvent. In addition to high resolution models of these oligomers, this study provides support for the conformational selection mechanism of A? peptide self-assembly.

SUBMITTER: Tran L

PROVIDER: S-EPMC4751476 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Structure of ring-shaped Aβ₄₂ oligomers determined by conformational selection.

Tran Linh L Basdevant Nathalie N Prévost Chantal C Ha-Duong Tâp T

Scientific reports 20160212

The oligomerization of amyloid beta (Aβ) peptides into soluble non-fibrillar species plays a critical role in the pathogenesis of Alzheimer's disease. However, it has been challenging to characterize the tertiary and quaternary structures of Aβ peptides due to their disordered nature and high aggregation propensity. In this work, replica exchange molecular dynamics simulations were used to explore the conformational space of Aβ42 monomer. Among the most populated transient states, we identified ...[more]

PMID: 26868929

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