Further exploration of the conformational space of α-synuclein fibrils: solid-state NMR assignment of a high-pH polymorph

Biomol NMR Assign. 2016 Apr;10(1):5-12. doi: 10.1007/s12104-015-9628-9. Epub 2015 Aug 30.

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.

Keywords: Polymorphism; Solid-state NMR; Synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Hydrogen-Ion Concentration
  • Mice
  • Nuclear Magnetic Resonance, Biomolecular*
  • Protein Isoforms / chemistry
  • Protein Structure, Secondary
  • alpha-Synuclein / chemistry*

Substances

  • Protein Isoforms
  • alpha-Synuclein