The differential solvent exposure of N-terminal residues provides "fingerprints" of alpha-synuclein fibrillar polymorphs.

ABSTRACT: Synucleinopathies are neurodegenerative diseases characterized by the presence of intracellular deposits containing the protein alpha-synuclein (aSYN) within patients' brains. It has been shown that aSYN can form structurally distinct fibrillar assemblies, also termed polymorphs. We previously showed that distinct aSYN polymorphs assembled in vitro, named fibrils, ribbons, and fibrils 91, differentially bind to and seed the aggregation of endogenous aSYN in neuronal cells, which suggests that distinct synucleinopathies may arise from aSYN polymorphs. In order to better understand the differential interactions of aSYN polymorphs with their partner proteins, we mapped aSYN polymorphs surfaces. We used limited proteolysis, hydrogen-deuterium exchange, and differential antibody accessibility t

SUBMITTER: Landureau M 

PROVIDER: S-EPMC8163981 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature