Pulsed Hydrogen-Deuterium Exchange Illuminates the Aggregation Kinetics of α-Synuclein, the Causative Agent for Parkinson's Disease.

ABSTRACT: α-Synuclein (aS) forms toxic intermediates ranging from small oligomers and protofibrils to large amyloid fibrils. Understanding the time course of aS fibril formation and the role played by its regions is critical for therapeutic intervention. Here, we used pulsed hydrogen-deuterium exchange and mass spectrometry (HDX-MS) for the first time to probe kinetic intermediates of the full aS aggregation in vitro, achieving kinetic snapshots containing spatially resolved protein information about critical stages. Monitoring the resultant mass shifts shows distinct binomial abundances for two main exchange profiles: one that represents a fast-exchanging, solvent-accessible species and another with a more protected nature. We show using a series of proteolytic peptides from the full protein that s

SUBMITTER: Illes-Toth E 

PROVIDER: S-EPMC6013392 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature