Further exploration of the conformational space of α-synuclein fibrils: solid-state NMR assignment of a high-pH polymorph.
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.
['Verasdonck|Joeri|J|', 'Bousset|Luc|L|', 'Gath|Julia|J|', 'Melki|Ronald|R|', 'Böckmann|Anja|A|', 'Meier|Beat H|BH|']
D000595:Amino Acid Sequence D000818:Animals D006863:Hydrogen-Ion Concentration D051379:Mice D019906:Nuclear Magnetic Resonance, Biomolecular D020033:Protein Isoforms D017433:Protein Structure, Secondary D051844:alpha-Synuclein
Solid-state NMR Polymorphism Synuclein