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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

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

Esteban-Martín Santiago S Silvestre-Ryan Jordi J Bertoncini Carlos W CW Salvatella Xavier X

Biophysical journal 20130901 5

Structural conversion of the presynaptic, intrinsically disordered protein α-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 α-synuclein involving amino acid residues that are, in the fibrillar state, part of β-strands. Importantly, this pattern of pairwise interactions does not correspond to that found in t ...[more]

PMID: 24010662

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