Familial Mutations May Switch Conformational Preferences in α-Synuclein Fibrils.

ABSTRACT: The pathogenesis of Parkinson's disease is closely associated with the aggregation of the α-synuclein protein. Several familial mutants have been identified and shown to affect the aggregation kinetics of α-synuclein through distinct molecular mechanisms. Quantitative evaluation of the relative stabilities of the wild type and mutant fibrils is crucial for understanding the aggregation process and identifying the key component steps. In this work, we examined two topologically different α-synuclein fibril structures that are either determined by solid-state NMR method or modeled based on solid-state NMR data, and characterized their conformational properties and thermodynamic stabilities using molecular dynamics simulations. We show that the two fibril morphologies have comparable size, so

SUBMITTER: Xu L 

PROVIDER: S-EPMC7900905 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature