Diverse metastable structures formed by small oligomers of α-synuclein probed by force spectroscopy.

ABSTRACT: Oligomeric aggregates are widely suspected as toxic agents in diseases caused by protein aggregation, yet they remain poorly characterized, partly because they are challenging to isolate from a heterogeneous mixture of species. We developed an assay for characterizing structure, stability, and kinetics of individual oligomers at high resolution and sensitivity using single-molecule force spectroscopy, and applied it to observe the formation of transient structured aggregates within single oligomers of α-synuclein, an intrinsically-disordered protein linked to Parkinson's disease. Measurements of the molecular extension as the proteins unfolded under tension in optical tweezers revealed that even small oligomers could form numerous metastable structures, with a surprisingly broad range of s

SUBMITTER: Neupane K 

PROVIDER: S-EPMC3901707 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature