Lipid-dependent conformational dynamics underlie the functional versatility of T-cell receptor  

作　　者：Xingdong Guo Chengsong Yan Hua Li Wenmao Huan Xiaoshan Shi Min Huang Yingfang Wang Weiling Pan Mingjun Cai Lunyi Li Wei Wu Yibing Bai Chi Zhang Zhijun Liu Xinyan Wang Xiaohui F Zhang Chun Tang Hongda Wang Wanli Liu Bo Ouyang Catherine C Wong Yi Cao Chenqi Xu 

机构地区：[1]State Key Laboratory of Molecular Biology, Shanghai Science Research Center, CAS Center for Excellence in Molecular Ceil Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China [2]Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Nanjing, Jiangsu 210093, China [3]State Key Laboratory of Eleetroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changc- hun, Jilin 130022, China [4]Bioengineering Program & Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA 18015, USA [5]State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei 430071, China [6]School of Life Sciences, Tsinghua Uni- versity, Beijing 100084, China [7]ShanghaiTech University, Shanghai 201210, China

出　　处：《Cell Research》2017年第4期505-525,共21页细胞研究（英文版）

基　　金：CX is funded by the Chinese Academy of Sciences （Strategic Priority Research Program XDB08020100）, and the National Natu- ral Science Foundation of China （31370860, 31425009, 31530022 and 31621003）. HL is funded by the Ministry of Science and Tech- noloy of China （2014CB541903） and the National Natural Science Foundation of China （31470734）. HW is funded by the Ministry of Science and Technoloy of China （2011 CB933600） and the National Natural Science Foundation of China （21373200）. XG is funded by China Postdoctoral Science Foundation （2015M580357）. NMR experiments, part of AFM and imaging experiments were performed at the National Center for Protein Science Shanghai. Part of imaging experiments was performed at the core facility for cell biology of Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences.

摘　　要：T-cell receptor-CD3 complex （TCR） is a versatile signaling machine that can initiate antigen-specific immune re- sponses based on various biochemical changes of CD3 cytoplasmic domains, but the underlying structural basis remains elusive. Here we developed biophysical approaches to study the conformational dynamics of CD3ε cytoplasmic domain （CD3εCD）. At the single-molecule level, we found that CD3εCD could have multiple conformational states with different openness of three functional motifs, i.e., ITAM, BRS and PRS. These conformations were generated because different regions of CD3εCD had heterogeneous lipid-binding properties and therefore had heterogeneous dynamics. Live-cell imaging experiments demonstrated that different antigen stimulations could stabilize CD3εCD at different conformations. Lipid-dependent conformational dynamics thus provide structural basis for the versatile signaling property of TCR.

关 键 词：T-cell receptor LIPID conformational dynamics atomic force microscopy nuclear magnetic resonance live-cellimaging 

分 类 号：Q510.2[生物学—生物化学] S943[农业科学—水产养殖]