title: Unlike twins: an NMR comparison of two α-synuclein polymorphs featuring different toxicity.
abstract: We structurally compare, using solid-state NMR, two different polymorphs of α-synuclein which, as established recently, display contrasting biochemical properties, toxicity, and tropism for cells. We show that both forms, which can each be produced as a pure polymorph, are greatly different in secondary structure. While β-sheets are the dominating secondary structure elements for both polymorphs, they are markedly divergent in terms of number of elements, as well as their distribution. We demonstrate that all identified β-sheets feature an in-register parallel stacking for both polymorphs. The two forms show a different molecular arrangement in the unit cell and distinct dynamic features, while sharing a highly flexible C-terminal domain. The use of reproducible, well-identified conditions for sample preparation and the recording of identical NMR experiments allows for a direct comparison of the results.
authors.affiliation: Physical Chemistry, ETH Zürich, Zurich, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Gath
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurales, UPR 3082 CNRS, Gif-sur-Yvette, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Bousset
authors.affiliation: Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS/Université de Lyon 1, Lyon, France.
authors.forename: Birgit
authors.initials: B
authors.lastname: Habenstein
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurales, UPR 3082 CNRS, Gif-sur-Yvette, France.
authors.forename: Ronald
authors.initials: R
authors.lastname: Melki
authors.affiliation: Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS/Université de Lyon 1, Lyon, France.
authors.forename: Anja
authors.initials: A
authors.lastname: Böckmann
authors.affiliation: Physical Chemistry, ETH Zürich, Zurich, Switzerland.
authors.forename: Beat H
authors.initials: BH
authors.lastname: Meier
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D018583:Pliability; D020033:Protein Isoforms / Q000737:chemistry / Q000633:toxicity; D017433:Protein Structure, Secondary; D051844:alpha-Synuclein / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D020033:Protein Isoforms; D051844:alpha-Synuclein