Lipid-dependent conformational dynamics underlie the functional versatility of T-cell receptor
Lipid-dependent conformational dynamics underlie the functional versatility of T-cell receptor
复制标题
脂质依赖性构象动力学是 T 细胞受体功能多样性的基础
DOI：
10.1038/cr.2017.42
复制
发表时间：
2017-04-01
期刊：
影响因子：
44.1
通讯作者：
Xu, Chenqi
中科院分区：
文献类型：
--
作者：
Guo, Xingdong;Yan, Chengsong;Xu, Chenqi
T细胞受体-CD 3复合物（TCR）是一种多功能的信号传导机制，可通过CD 3胞质结构域的各种生化变化启动抗原特异性免疫应答，但其结构基础尚不清楚。本研究采用生物物理方法研究了CD 3 β胞质结构域（CD 3 β（CD））的构象动力学。在单分子水平上，我们发现CD 3 β（CD）可以有多种构象状态，三种功能基序的开放程度不同，ITAM、BRS和PRS。这些构象的产生是因为CD 3 β（CD）的不同区域具有异质性脂质结合特性，因此具有异质性动力学。活细胞成像实验表明，不同的抗原刺激可以稳定在不同的构象的CD 3 γ（CD）。因此，脂质依赖性构象动力学为TCR的多功能信号传导特性提供了结构基础。
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 CD3 epsilon cytoplasmic domain (CD3 epsilon(CD)). At the single-molecule level, we found that CD3 epsilon(CD) 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 CD3 epsilon(CD) had heterogeneous lipid-binding properties and therefore had heterogeneous dynamics. Live-cell imaging experiments demonstrated that different antigen stimulations could stabilize CD3 epsilon(CD) at different conformations. Lipid-dependent conformational dynamics thus provide structural basis for the versatile signaling property of TCR.