Interplay of alpha-synuclein binding and conformational switching probed by single-molecule fluorescence.

ABSTRACT: We studied the coupled binding and folding of alpha-synuclein, an intrinsically disordered protein linked with Parkinson's disease. Using single-molecule fluorescence resonance energy transfer and correlation methods, we directly probed protein membrane association, structural distributions, and dynamics. Results revealed an intricate energy landscape on which binding of alpha-synuclein to amphiphilic small molecules or membrane-like partners modulates conformational transitions between a natively unfolded state and multiple alpha-helical structures. Alpha-synuclein conformation is not continuously tunable, but instead partitions into 2 main classes of folding landscape structural minima. The switch between a broken and an extended helical structure can be triggered by changing the concent

SUBMITTER: Ferreon AC 

PROVIDER: S-EPMC2667048 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature