The conformational stability of nonfibrillar amyloid-β peptide oligomers critically depends on the C-terminal peptide length.

ABSTRACT: The amyloid-β (Aβ) peptide is one key molecule in the pathogenesis of Alzheimer's disease. We investigated the conformational stability of a nonfibrillar tetrameric Aβ structure by molecular dynamics (MD) simulations revealing that the stability of the Aβ tetramer depends critically on the C-terminal length. In contrast to the Aβ17-40 tetramer, which proved to be instable, the simulations demonstrate structural integrity of the Aβ17-42 and Aβ17-43 tetramers. These differences in stability can be attributed to an extension of the middle strand of a three-stranded antiparallel β sheet through residues 41-43, only present in the longer Aβ species that aggregate faster and are more neurotoxic. Additional MD simulations demonstrate that this higher stability is also present in the monomers form

SUBMITTER: Socher E 

PROVIDER: S-EPMC3963130 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature