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Yet another polymorph of α-synuclein: solid-state sequential assignments

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Abstract

Parkinson’s disease is a neurological human proteinopathy, which is caused by the accumulation of protein aggregates of high molecular mass. α-Synuclein is a major component of these fibrillar, β-sheet rich, insoluble assemblies and is deposited in the form of amyloids. Structural characterization of amyloids is possible by solid-state NMR, although no atomic-resolution structure is available as of today. α-Synuclein, as many other pathology-related fibril-forming proteins, can form a number of different polymorphs that are sometimes tricky to obtain in pure form. Here, we describe the chemical shifts and secondary structure analysis of a polymorph that also adopts mainly β-sheet conformation, with a fibrillar core ranging from residues 38 to 94. In addition, residues 15–20 from the N-terminus found to be part of a rigid ordered β-sheet. The chemical shifts differ substantially from the polymorph we previously assigned.

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Acknowledgments

This work was supported by the Agence Nationale de la Recherche (ANR-11-BSV8-021-01), the ETH Zurich, the Swiss National Science Foundation (Grant 200020_124611), the Era-Net Neuron (project MIPROTRAN, ANR-08-NEUR-001-01) and the Centre National de la Recherche Scientifique. We also acknowledge support from the European Commission under the Seventh Framework Programme (FP7), contract Bio-NMR 261863.

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Authors and Affiliations

  1. Physical Chemistry, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland

    Julia Gath & Beat H. Meier

  2. Laboratoire d’Enzymologie et Biochimie Structurales, UPR 3082, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France

    Luc Bousset & Ronald Melki

  3. Institut de Biologie et Chimie des Protéines, UMR 5086, CNRS/Université de Lyon 1, 7 passage du Vercors, 69367, Lyon, France

    Birgit Habenstein & Anja Böckmann

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  1. Julia Gath
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  2. Luc Bousset
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  3. Birgit Habenstein
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  4. Ronald Melki
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  5. Beat H. Meier
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  6. Anja Böckmann
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Corresponding authors

Correspondence to Ronald Melki, Beat H. Meier or Anja Böckmann.

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Julia Gath and Luc Bousset have contributed equally to this work.

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Gath, J., Bousset, L., Habenstein, B. et al. Yet another polymorph of α-synuclein: solid-state sequential assignments. Biomol NMR Assign 8, 395–404 (2014). https://doi.org/10.1007/s12104-013-9526-y

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  • DOI: https://doi.org/10.1007/s12104-013-9526-y

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