The structural heterogeneity of α-synuclein is governed by several distinct subpopulations with interconversion times slower than milliseconds.

ABSTRACT: α-Synuclein plays an important role in synaptic functions by interacting with synaptic vesicle membrane, while its oligomers and fibrils are associated with several neurodegenerative diseases. The specific monomer structures that promote its membrane binding and self-association remain elusive due to its transient nature as an intrinsically disordered protein. Here, we use inter-dye distance distributions from bulk time-resolved Förster resonance energy transfer as restraints in discrete molecular dynamics simulations to map the conformational space of the α-synuclein monomer. We further confirm the generated conformational ensemble in orthogonal experiments utilizing far-UV circular dichroism and cross-linking mass spectrometry. Single-molecule protein-induced fluorescence enhancement mea

SUBMITTER: Chen J 

PROVIDER: S-EPMC8419013 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature