title: Conserved core of amyloid fibrils of wild type and A30P mutant α-synuclein.
abstract: The major component of neural inclusions that are the pathological hallmark of Parkinson's disease are amyloid fibrils of the protein α-synuclein (aS). Here we investigated if the disease-related mutation A30P not only modulates the kinetics of aS aggregation, but also alters the structure of amyloid fibrils. To this end we optimized the method of quenched hydrogen/deuterium exchange coupled to NMR spectroscopy and performed two-dimensional proton-detected high-resolution magic angle spinning experiments. The combined data indicate that the A30P mutation does not cause changes in the number, location and overall arrangement of β-strands in amyloid fibrils of aS. At the same time, several residues within the fibrillar core retain nano-second dynamics. We conclude that the increased pathogenicity related to the familial A30P mutation is unlikely to be caused by a mutation-induced change in the conformation of aS aggregates.
authors.affiliation: Department for NMR based Structural Biology, Max Planck Institute for Biophysical Chemistry, D-37077, Goettingen, Germany.
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Cho
authors.forename: Hai-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Claudio O
authors.initials: CO
authors.lastname: Fernandez
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein