Identification of fibril-like tertiary contacts in soluble monomeric ?-synuclein.

ABSTRACT: Structural conversion of the presynaptic, intrinsically disordered protein ?-synuclein into amyloid fibrils underlies neurotoxicity in Parkinson's disease. The detailed mechanism by which this conversion occurs is largely unknown. Here, we identify a discrete pattern of transient tertiary interactions in monomeric ?-synuclein involving amino acid residues that are, in the fibrillar state, part of ?-strands. Importantly, this pattern of pairwise interactions does not correspond to that found in the amyloid state. A redistribution of this network of fibril-like contacts must precede aggregation into the amyloid structure.

SUBMITTER: Esteban-Martin S 

PROVIDER: S-EPMC3762368 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature