A relationship between the transient structure in the monomeric state and the aggregation propensities of α-synuclein and β-synuclein.

ABSTRACT: α-Synuclein is an intrinsically disordered protein whose aggregation is implicated in Parkinson's disease. A second member of the synuclein family, β-synuclein, shares significant sequence similarity with α-synuclein but is much more resistant to aggregation. β-Synuclein is missing an 11-residue stretch in the central non-β-amyloid component region that forms the core of α-synuclein amyloid fibrils, yet insertion of these residues into β-synuclein to produce the βSHC construct does not markedly increase the aggregation propensity. To investigate the structural basis of these different behaviors, quantitative nuclear magnetic resonance data, in the form of paramagnetic relaxation enhancement-derived interatomic distances, are combined with molecular dynamics simulations to generate ensemble

SUBMITTER: Allison JR 

PROVIDER: S-EPMC4245978 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature