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DOI | 10.1038/s41467-019-11601-2 |
An allosteric site in the T-cell receptor C beta domain plays a critical signalling role | |
Natarajan, Kannan1; McShan, Andrew C.2; Jiang, Jiansheng1; Kumirov, Vlad K.2; Wang, Rui1; Zhao, Huaying3; Schuck, Peter3; Tilahun, Mulualem E.1; Boyd, Lisa F.1; Ying, Jinfa4; Bax, Ad4; Margulies, David H.1; Sgourakis, Nikolaos G.2 | |
2019-08-16 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | The molecular mechanism through which the interaction of a clonotypic alpha beta T-cell receptor (TCR) with a peptide-loaded major histocompatibility complex (p/MHC) leads to T-cell activation is not yet fully understood. Here we exploit a high-affinity TCR (B4.2.3) to examine the structural changes that accompany binding to its p/MHC ligand (P18-I10/H2-D-d). In addition to conformational changes in complementarity-determining regions (CDRs) of the TCR seen in comparison of unliganded and bound X-ray structures, NMR characterization of the TCR beta-chain dynamics reveals significant chemical shift effects in sites removed from the MHC-binding site. Remodelling of electrostatic interactions near the C beta H3 helix at the membrane-proximal face of the TCR, a region implicated in interactions with the CD3 co-receptor, suggests a possible role for an allosteric mechanism in TCR signalling. The contribution of these TCR residues to signal transduction is supported by mutagenesis and T-cell functional assays. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000401405000001 |
WOS关键词 | CONFORMATIONAL-CHANGE ; NMR-SPECTROSCOPY ; QUANTUM NMR ; COMPLEX ; PEPTIDE ; MHC ; MOLECULES ; SOFTWARE ; REVEALS ; ANTIGEN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204500 |
专题 | 资源环境科学 |
作者单位 | 1.NIAID, Mol Biol Sect, Lab Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA; 2.Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA; 3.Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA; 4.NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA |
推荐引用方式 GB/T 7714 | Natarajan, Kannan,McShan, Andrew C.,Jiang, Jiansheng,et al. An allosteric site in the T-cell receptor C beta domain plays a critical signalling role[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Natarajan, Kannan.,McShan, Andrew C..,Jiang, Jiansheng.,Kumirov, Vlad K..,Wang, Rui.,...&Sgourakis, Nikolaos G..(2019).An allosteric site in the T-cell receptor C beta domain plays a critical signalling role.NATURE COMMUNICATIONS,8. |
MLA | Natarajan, Kannan,et al."An allosteric site in the T-cell receptor C beta domain plays a critical signalling role".NATURE COMMUNICATIONS 8(2019). |
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