Local and Global Dynamics in Intrinsically Disordered Synuclein.
Local and Global Dynamics in Intrinsically Disordered Synuclein.
复制标题
本质无序突触核蛋白的局部和全局动态。
作者：
N. Rezaei;G. Parigi;Andrea Soranno;A. Holla;S. Becker;B. Schuler;C. Luchinat;M. Zweckstetter
本质无序蛋白质（IDP）经历多种运动，很难用单一的实验技术来表征。在这里，我们结合了高场和低场核自旋弛豫、纳秒荧光相关光谱（nsFCS）和α-突触核蛋白（一种与帕金森病有关的IDP）的长分子动力学模拟，以获得其构象动力学的全面图像。综合分析表明，由局部二面角波动和 Ramachandran 亚态内部和之间的构象采样引起的低于 2 ns 的快速运动使大部分骨干 N-H 方向记忆去相关。然而，相关时间高达大约的慢动作。来自片段动力学的 13 ns 存在于整个 α-突触核蛋白链中，特别是在其 C 末端结构域中，全局链重构发生在大约 13ns 的时间尺度上。 60 ns。我们的研究展示了一种强大的策略来确定不同时间和长度范围内 IDP 中残基特异性蛋白质动态。
Intrinsically disordered proteins (IDPs) experience a diverse spectrum of motions that are difficult to characterize with a single experimental technique. Herein we combine high- and low-field nuclear spin relaxation, nanosecond fluorescence correlation spectroscopy (nsFCS), and long molecular dynamics simulations of alpha-synuclein, an IDP involved in Parkinson disease, to obtain a comprehensive picture of its conformational dynamics. The combined analysis shows that fast motions below 2 ns caused by local dihedral angle fluctuations and conformational sampling within and between Ramachandran substates decorrelate most of the backbone N-H orientational memory. However, slow motions with correlation times of up to ca. 13 ns from segmental dynamics are present throughout the alpha-synuclein chain, in particular in its C-terminal domain, and global chain reconfiguration occurs on a timescale of ca. 60 ns. Our study demonstrates a powerful strategy to determine residue-specific protein dynamics in IDPs at different time and length scales.
DOI：
10.1039/c5cp06197k
发表时间：
2016-02-17
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Gill ML;Byrd RA;Palmer AG III
通讯作者：
Palmer AG III
DOI：
10.1073/pnas.160259697
发表时间：
2000-08-01
影响因子：
11.1
作者：
Shoemaker, BA;Portman, JJ;Wolynes, PG
通讯作者：
Wolynes, PG