Bisaglia Marco, Mammi Stefano, Bubacco Luigi
Department of Biology, University of Padova, Via U. Bassi 58B, 35121, Padova, Italy.
FASEB J. 2009 Feb;23(2):329-40. doi: 10.1096/fj.08-119784. Epub 2008 Oct 23.
Alpha-synuclein is an intrinsically unfolded protein that can adopt a partially helical structure when it interacts with different lipid membranes. Its pathological relevance is linked to its involvement in several neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, and dementia with Lewy bodies. Typical of such ailments is the presence of alpha-synuclein aggregates in a beta-structure that can be soluble or precipitate. This review focuses on the structural knowledge acquired in recent years on the various conformations accessible to alpha-synuclein and to its pathologically relevant mutants. Furthermore, the role of the different variables of the chemical environments that govern the equilibria among the accessible conformations is also reviewed. The hypotheses that rationalize the relevance of the individual structural features and conformations for the physiological function of the protein or for its purported pathological role are described and compared.
α-突触核蛋白是一种内在无序蛋白，当它与不同的脂质膜相互作用时可形成部分螺旋结构。其病理相关性与其参与多种神经退行性疾病有关，包括帕金森病、阿尔茨海默病和路易体痴呆。这类疾病的典型特征是存在β结构的α-突触核蛋白聚集体，这些聚集体可以是可溶性的或沉淀性的。本综述聚焦于近年来所获得的关于α-突触核蛋白及其病理相关突变体可及的各种构象的结构知识。此外，还综述了控制可及构象之间平衡的化学环境的不同变量的作用。描述并比较了使蛋白质的各个结构特征和构象与生理功能或其假定的病理作用相关的假设。
