《生命科学》 2025, 37(7): 868-877

核磁共振研究蛋白质不同时间尺度的动力学与功能关系的实验方法和应用进展

薛红娟¹ , 詹　伟¹ , 马荣声² , 余　诗³ , 张胜男⁴ , 黎彦璟⁵ , 赵琳琳⁵ , 李　华⁵ , 刘东升⁶ , 宋乡飞⁷ , 刘志军^1,*

¹中国科学院上海高等研究院国家蛋白质科学研究(上海)设施，上海 201210 ²中国科学技术大学生 命科学学院，合肥 230026 ³复旦大学化学系，上海 200433 ⁴中国科学院上海有机化学研究所， 生物与化学交叉研究中心，上海 200032 ⁵中国科学院分子细胞科学卓越创新中心，上海 200031 ⁶上海科技大学iHuman研究所，上海 201210 ⁷中国科学院青岛生物能源与过程研究所，青岛 266101

摘　要：

本文概述了研究蛋白质动力学的核磁共振波谱的基本概念和方法，并分析了其在不同时间尺度的应用能力。结合过去十年蛋白质设施核磁共振分析系统涉及的蛋白质动力学研究成果，阐述了近年来在蛋白质结构、动力学、相互作用与功能关系研究的进展。文章重点讨论了以下六个方面：(1)天然无规蛋白质(IDP/IDR) 的动力学和相互作用与功能的关系；(2)甲基转移酶的构象动态性及功能调控与催化特异性的关系；(3)单次跨膜蛋白质的胞外区域动态结构、跨膜区多聚结构与受体自抑制及跨膜信号传递的关系；(4)免疫受体近膜区及其胞内区域的动态相互作用与受体活化调控的关系；(5)GPCR 膜蛋白的大幅度动态性与多步骤配体选择性的关系；(6)细胞原位环境蛋白质的动力学和相互作用与蛋白质折叠的关系。

通讯作者：刘志军 , Email:liuzhijun@sari.ac.cn

NMR experimental methods and applicational progress in studying the relationship of protein dynamics and function at different time scales

XUE Hong-Juan¹ , ZHAN Wei¹ , MA Rong-Sheng² , YU Shi³ , ZHANG Sheng-Nan⁴ , LI Yan-Jing⁵ , ZHAO Lin-Lin⁵ , LI Hua⁵ , LIU Dong-Sheng⁶ , SONG Xiang-Fei⁷ , LIU Zhi-Jun^1,*

¹National Facility for Protein Science (Shanghai), Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China ²School of Life Sciences, University of Science and Technology of China, Hefei 230026, China ³Department of Chemistry, Fudan University, Shanghai 200433, China ⁴Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China ⁵Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China ⁶iHuman Research Institute, ShanghaiTech University, Shanghai 201210, China ⁷Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China

Abstract:

This article provides an overview of the basic concepts and methods of nuclear magnetic resonance (NMR) spectroscopy for studying protein dynamics and its application capabilities at different time scales. Based on the research results of protein dynamics related to our NMR system of NFPS in the past decade, this article elaborates on the recent progress in the study of protein structure, dynamics, interactions, and functional relationships. It focuses on the following six aspects: (1) the dynamics, interactions, and functional relationships of intrinsic disorded proteins (IDP/IDR); (2) The relationship between the conformational dynamics and functional regulation of methyltransferase and its catalytic specificity; (3) The relationship between the dynamic structures of the extracellular region of a single transmembrane protein, the multimeric structure of the transmembrane region, receptor self inhibition, and transmembrane signal transduction; (4) The dynamic interaction between the near membrane and intracellular regions of immune receptors and its regulation of receptor activation; (5) The relationship between the significant dynamics of GPCR membrane proteins and its multi-step ligand selectivity; (6) The relationship between the dynamics, interactions and folding of proteins in situ by In-Cell NMR methods.

Communication Author：LIU Zhi-Jun , Email:liuzhijun@sari.ac.cn