The structures of the E22Δ mutant-type amyloid-β alloforms and the impact of E22Δ mutation on the structures of the wild-type amyloid-β alloforms.

ABSTRACT: Structural differences between the intrinsically disordered fibrillogenic wild-type Aβ40 and Aβ42 peptides are linked to Alzheimer's disease. Recently, the E22Δ genetic missense mutation was detected in patients exhibiting Alzheimer's-disease type dementia. However, detailed knowledge about the E22Δ mutant-type Aβ40 and Aβ42 alloform structures as well as the differences from the wild-type Aβ40 and Aβ42 alloform structures is currently lacking. In this study, we present the structures of the E22Δ mutant-type Aβ40 and Aβ42 alloforms as well as the impact of E22Δ mutation on the wild-type Aβ40 and Aβ42 alloform structures. For this purpose, we performed extensive microsecond-time scale parallel tempering molecular dynamics simulations coupled with thermodynamic calculations. For studying the

SUBMITTER: Coskuner O 

PROVIDER: S-EPMC3582298 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature