Structure of amyloid β_25-35 in lipid environment and cholesterol-dependent membrane pore formation.

ABSTRACT: The amyloid β (Aβ) peptide and its shorter variants, including a highly cytotoxic Aβ_25-35 peptide, exert their neurotoxic effect during Alzheimer's disease by various mechanisms, including cellular membrane permeabilization. The intrinsic polymorphism of Aβ has prevented the identification of the molecular basis of Aβ pore formation by direct structural methods, and computational studies have led to highly divergent pore models. Here, we have employed a set of biophysical techniques to directly monitor Ca²⁺-transporting Aβ_25-35 pores in lipid membranes, to quantitatively characterize pore formation, and to identify the key structural features of the pore. Moreover, the effect of membrane cholesterol on pore formation and the structure of Aβ_25-35

SUBMITTER: Kandel N 

PROVIDER: S-EPMC6389947 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature