Journal Article

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

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

2017

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Amino Acid Sequence / Antigens - metabolism / Binding Sites / Biomedical and Life Sciences / CD3 / CD3 Complex - chemistry / Cell Biology / Cell Survival / Humans / Kinetics / Life Sciences / Lipids - chemistry / Magnetic Resonance Spectroscopy / Micelles / Microscopy, Atomic Force / Original / original-article / Protein Conformation / Receptors, Antigen, T-Cell - chemistry / Receptors, Antigen, T-Cell - metabolism / Solutions / Solvents - chemistry / Surface Plasmon Resonance / T-Lymphocytes - metabolism / T细胞受体 / 依赖性 / 多功能性 / 构象动力学 / 结合特性 / 结构基础 / 脂质