Verasdonck Joeri, Bousset Luc, Gath Julia, Melki Ronald, Böckmann Anja, Meier Beat H
Physical Chemistry, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland.
Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
Biomol NMR Assign. 2016 Apr;10(1):5-12. doi: 10.1007/s12104-015-9628-9. Epub 2015 Aug 30.
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.
多态性是蛋白质原纤维常见且重要的现象，与朊病毒及其他神经退行性疾病中毒株的出现有关。帕金森病是一种常见的神经退行性病变，与路易小体的形成密切相关。这些沉积物主要由富含β折叠的纤维状α-突触核蛋白组成。已知α-突触核蛋白会形成多种不同的多态体，呈现出不同的结构特征。在此，我们描述了在高于生理pH条件下形成纤维的一种多态体的化学位移归属，并推导了其二级结构。纤维状核心包含40 - 95位残基，C端和N端均未显示出任何有序、刚性的部分。这些化学位移与之前在中性pH条件下形成纤维的已归属多态体所记录的化学位移相似。
