Impact of Cholesterol Concentration and Lipid Phase on Structure and Fluctuation of Amyloid Precursor Protein.

ABSTRACT: Elevated levels of cellular cholesterol have been identified as one factor contributing to the onset of Alzheimer's disease (AD). Specific interaction between cholesterol and the amyloid precursor protein (APP), investigated via NMR experiments and computational studies, has been proposed to play a critical role in the processing of APP by secretases and the biogenesis of amyloid-β (Aβ) protein. We present all-atom molecular dynamics simulations of the 40-residue congener of the C-terminal domain of APP, C99_16-55 (C99), in cholesterol-enriched DMPC lipid bilayers. We investigated the effect of cholesterol concentration on the conformational ensemble of wild-type C99 and C99-cholesterol associations at the low pH of endosomal environments, at which residues E22 and D23 are neutra

SUBMITTER: Pantelopulos GA 

PROVIDER: S-EPMC7958706 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature