Transmembrane fragment structures of amyloid precursor protein depend on membrane surface curvature.

ABSTRACT: The amyloid β (Aβ) peptide associated with Alzheimer's disease results from processing of the amyloid precursor protein (APP) by secretases. Cleavage of APP by β-secretase produces a 99 amino acid C-terminal fragment of APP (C99) consisting of a single transmembrane (TM) helix. Simulations of C99 congeners and structural studies of C99 in surfactant micelles and lipid vesicles have shown that a key peptide structural motif is a prominent "GG kink," centered at two glycines dividing the TM helix. The flexibility of the GG kink is important in the processing of C99 by γ-secretase. We performed multiscale simulations of C99(15-55) in a DPC surfactant micelle and POPC lipid bilayer in order to elucidate the role of membrane surface curvature in modulating the peptide structure. C99(15-55) in a

SUBMITTER: Dominguez L 

PROVIDER: S-EPMC3928069 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature