title: Further exploration of the conformational space of α-synuclein fibrils: solid-state NMR assignment of a high-pH polymorph.
abstract: Polymorphism is a common and important phenomenon for protein fibrils which has been linked to the appearance of strains in prion and other neurodegenerative diseases. Parkinson disease is a frequently occurring neurodegenerative pathology, tightly associated with the formation of Lewy bodies. These deposits mainly consist of α-synuclein in fibrillar, β-sheet-rich form. α-synuclein is known to form numerous different polymorphs, which show distinct structural features. Here, we describe the chemical shift assignments, and derive the secondary structure, of a polymorph that was fibrillized at higher-than-physiological pH conditions. The fibrillar core contains residues 40-95, with both the C- and N-terminus not showing any ordered, rigid parts. The chemical shifts are similar to those recorded previously for an assigned polymorph that was fibrillized at neutral pH.
authors: Physical Chemistry, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland.
authors: Joeri
authors: J
authors: Verasdonck
authors: Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors: Luc
authors: L
authors: Bousset
authors: Physical Chemistry, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland.
authors: Julia
authors: J
authors: Gath
authors: Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors: Ronald
authors: R
authors: Melki
authors: Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS/Université de Lyon 1, 7, passage du Vercors, 69367, Lyon, France.
authors: Anja
authors: A
authors: Böckmann
authors: Physical Chemistry, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland. Beme@ethz.ch.
authors: Beat H
authors: BH
authors: Meier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006863:Hydrogen-Ion Concentration; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D020033:Protein Isoforms / Q000737:chemistry; D017433:Protein Structure, Secondary; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D020033:Protein Isoforms; D051844:alpha-Synuclein
keywords: Polymorphism; Solid-state NMR; Synuclein