Functional protein dynamics on uncharted time scales detected by nanoparticle-assisted NMR spin relaxation
Functional protein dynamics on uncharted time scales detected by nanoparticle-assisted NMR spin relaxation
复制标题
DOI：
10.1126/sciadv.aax5560
复制
发表时间：
2019-08
期刊：
影响因子：
13.6
通讯作者：
Mouzhe Xie;Lei Yu;Lei Bruschweiler‐Li;Xinyao Xiang;Alexandar L. Hansen;R. Brüschweiler
中科院分区：
文献类型：
--
作者：
Mouzhe Xie;Lei Yu;Lei Bruschweiler‐Li;Xinyao Xiang;Alexandar L. Hansen;R. Brüschweiler
纳米颗粒辅助蛋白质核磁共振打开了观察纳秒至微秒范围内新型功能动力学的窗口。蛋白质功能关键取决于内在的内部动力学，这以不同的方式表现出来，例如调节蛋白质识别和催化的环运动。在生理条件下，动态过程发生在从亚皮秒到秒的广泛时间尺度上。溶液中常用的 NMR 自旋弛豫可提供有关非常快和慢速运动的宝贵信息，但对超过蛋白质翻滚相关时间的中间纳秒到微秒范围不敏感。目前，人们对这些运动的性质和功能作用知之甚少。这里展示了当研究存在纳米颗粒的蛋白质时，横向自旋弛豫如何在原子分辨率下对这些运动变得极其敏感。这种新颖的跨学科方法的应用揭示了以前无法观察到的、参与功能关键的蛋白质-蛋白质相互作用和蛋白质-钙离子识别的环的大规模动态。
Nanoparticle-assisted protein NMR opens window to observation of novel functional dynamics in the nano- to microsecond range. Protein function depends critically on intrinsic internal dynamics, which is manifested in distinct ways, such as loop motions that regulate protein recognition and catalysis. Under physiological conditions, dynamic processes occur on a wide range of time scales from subpicoseconds to seconds. Commonly used NMR spin relaxation in solution provides valuable information on very fast and slow motions but is insensitive to the intermediate nanosecond to microsecond range that exceeds the protein tumbling correlation time. Presently, very little is known about the nature and functional role of these motions. It is demonstrated here how transverse spin relaxation becomes exquisitely sensitive to these motions at atomic resolution when studying proteins in the presence of nanoparticles. Application of this novel cross-disciplinary approach reveals large-scale dynamics of loops involved in functionally critical protein-protein interactions and protein-calcium ion recognition that were previously unobservable.