Volume 27, No 4, Apr 2017

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 27 Issue 4, April 2017: 505-525

ORIGINAL ARTICLES

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

Xingdong Guo^1,*, Chengsong Yan^1,*, Hua Li^1,*, Wenmao Huang^2,*, Xiaoshan Shi¹, Min Huang¹, Yingfang Wang¹, Weiling Pan¹, Mingjun Cai³, Lunyi Li¹, Wei Wu¹, Yibing Bai¹, Chi Zhang¹, Zhijun Liu¹, Xinyan Wang¹, Xiaohui F Zhang⁴, Chun Tang⁵, Hongda Wang³, Wanli Liu⁶, Bo Ouyang¹, Catherine C Wong¹, Yi Cao² and Chenqi Xu^1,7

¹State Key Laboratory of Molecular Biology, Shanghai Science Research Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China
²Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Nanjing, Jiangsu 210093, China
³State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China
⁴Bioengineering Program & Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA 18015, USA
⁵State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
⁶School of Life Sciences, Tsinghua University, Beijing 100084, China
⁷ShanghaiTech University, Shanghai 201210, China Correspondence: Chenqi Xu, E-mail: cqxu@sibcb.ac.cn; Yi Cao,(caoyi@nju.edu.cn)

T-cell receptor-CD3 complex (TCR) is a versatile signaling machine that can initiate antigen-specific immune responses 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.

10.1038/cr.2017.42

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