Conformational-Sensitive Fast Photochemical Oxidation of Proteins and Mass Spectrometry Characterize Amyloid Beta 1-42 Aggregation.

ABSTRACT: Preventing and treating Alzheimer's disease require understanding the aggregation of amyloid beta 1-42 (Aβ1-42) to give oligomers, protofibrils, and fibrils. Here we describe footprinting of Aβ1-42 by hydroxyl radical-based fast photochemical oxidation of proteins (FPOP) and mass spectrometry (MS) to monitor the time-course of Aβ1-42 aggregation. We resolved five distinct stages characterized by two sigmoidal behaviors, showing the time-dependent transitions of monomers-paranuclei-protofibrils-fibrillar aggregates. Kinetic modeling allows deciphering the amounts and interconversion of the dominant Aβ1-42 species. Moreover, the irreversible footprinting probe provides insights into the kinetics of oligomerization and subsequent fibrillar growth by allowing the conformational changes of Aβ1-

SUBMITTER: Li KS 

PROVIDER: S-EPMC5221481 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature