Atomic Resolution Insights into pH Shift Induced Deprotonation Events in LS-Shaped Aβ(1-42) Amyloid Fibrils.

ABSTRACT: Alzheimer's disease is a neurodegenerative disorder associated with the deposition of misfolded aggregates of the amyloid-β protein (Aβ). Aβ(1-42) is one of the most aggregation-prone components in senile plaques of AD patients. We demonstrated that relatively homogeneous Aβ(1-42) fibrils with one predominant fold visible in solid-state NMR spectra can be obtained at acidic pH. The structure of these fibrils differs remarkably from some other polymorphs obtained at neutral pH. In particular, the entire N-terminal region is part of the rigid fibril core. Here, we investigate the effects of a pH shift on the stability and the fold of these fibrils at higher pH values. Fibril bundling at neutral pH values renders cryo-EM studies impractical, but solid-state NMR spectroscopy, molecular dynamic

SUBMITTER: Becker N 

PROVIDER: S-EPMC9896559 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature