title: Identification of fibril-like tertiary contacts in soluble monomeric α-synuclein.
abstract: 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 the amyloid state. A redistribution of this network of fibril-like contacts must precede aggregation into the amyloid structure.
authors.affiliation: Joint BSC-IRB Research Programme in Computational Biology, Barcelona Supercomputing Center BSC, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Esteban-Martín
authors.forename: Jordi
authors.initials: J
authors.lastname: Silvestre-Ryan
authors.forename: Carlos W
authors.initials: CW
authors.lastname: Bertoncini
authors.forename: Xavier
authors.initials: X
authors.lastname: Salvatella
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D012995:Solubility; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein