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

• Published in: Biomolecular NMR assignments Vol. 8; no. 2; pp. 395 - 404
• Main Authors: Gath, Julia, Bousset, Luc, Habenstein, Birgit, Melki, Ronald, Meier, Beat H., Böckmann, Anja
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2014; Springer
• Subjects: alpha-Synuclein - chemistry; Amino Acid Sequence; Biochemistry; Biological and Medical Physics; Biophysics; Humans; Life Sciences; Molecular Sequence Data; Neurons and Cognition; Nuclear Magnetic Resonance, Biomolecular; Physics; Physics and Astronomy; Polymer Sciences; Protein Structure, Secondary; Assignments; α-Synuclein; Solid-state NMR; Secondary structure; Fibrils
• ISSN: 1874-2718; 1874-270X
• DOI: 10.1007/s12104-013-9526-y

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.