Ubiquitin binds the amyloid β peptide and interferes with its clearance pathways.

ABSTRACT: Several lines of evidence point to a compromised proteostasis associated with a reduction of the Ubiquitin Proteasome System (UPS) activity in patients affected by Alzheimer's Disease (AD) and suggest that the amyloid β peptide (Aβ) is an important player in the game. Inspired also by many reports, underlining the presence of ubiquitin (Ub) in the amyloid plaques of AD brains, here we set out to test whether Ub may bind the Aβ peptide and have any effect on its clearance pathways. By using an integrated array of MALDI-TOF/UPLC-HRMS, fluorescence, NMR, SPR, Microscale Thermophoresis (MST) and molecular dynamics studies, we consistently demonstrated that Aβ40 binds Ub with a 1 : 1 stoichiometry and K _d in the high micromolar range. In particular, we show that the N-terminal

SUBMITTER: Bellia F 

PROVIDER: S-EPMC6419943 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature