Effects of Mutations on the Reconfiguration Rate of α-Synuclein.

ABSTRACT: It is still poorly understood why α-synuclein, the intrinsically disordered protein involved in Parkinson's and other neurodegenerative diseases, is so prone to aggregation. Recent work has shown a correlation between the aggregation rate and the rate of diffusional reconfiguration by varying temperature and pH. Here we examine the effects of several point mutations in the sequence on the conformational ensemble and reconfiguration rate. We find that at lower temperatures the PD causing aggregation enhancing mutations slow down and aggregation reducing mutations drastically speed up intramolecular diffusion, as compared to the wild type sequence. However, at higher temperatures, one of three familial mutations that enhance aggregation slows intramolecular diffusion while non-natural mutati

SUBMITTER: Acharya S 

PROVIDER: S-EPMC4836914 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature