NMR在ɑ-synuclein的结构及相互作用研究中的应用

Application of NMR in the Studies of Structure and Interactions of ?-Synuclein

α-synuclein(AS)是一种和帕金森病(PD)密切相关的天然无结构蛋白,是PD标志物路易小体(LB)的主要成分.AS异常聚集和纤维化被认为是引起PD的主要原因之一,因而针对其结构、聚集和功能的研究一直是国际上的热点.核磁共振(NMR)技术能获得具有原子分辨率的蛋白质结构和动态信息,尤其适合研究其它生物物理方法难以研究的天然无结构蛋白.该综述主要讨论NMR技术结合其他技术手段在AS的结构、聚集机制、以及与生物膜、金属离子和其它蛋白质相互作用研究中的应用.这些研究结果为探索PD的发病机制提供了有益的线索.

α-synuclein （AS） is natively unfolded protein, and has the potential to aggregate and assemble into fibrils. AS fibril is the major component of Lewy bodies （LB）, the hallmark of neurodegenerative diseases such as Parkinson＇s disease （PD）. Many previous studies have studied the structure and functions of AS, hoping toshed a light on the pathogenesis of PD. Compared to the other methods, nuclear magnetic resonance （NMR） has many advantages in studying natively unfolded proteins, and can provide atom-level structural and dynamic information of these proteins. This review focuses on the applications of NMR, combined with other techniques, in the studies on the structure, aggregation mechanisms, membrane interactions, metal ion interactions, and protein interactions of AS.