9CI8

T cell receptor complex

9CI8 の概要

• エントリーDOI: 10.2210/pdb9ci8/pdb
• EMDBエントリー: 45614
• 分子名称: UCHT1 Fab, UCHT1 Fab chain 2, T-cell surface glycoprotein CD3 zeta chain, ... (8 entities in total)
• 機能のキーワード: t cell receptor t cell immunity, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 163298.76

構造登録者

Gully, B.S.,Rossjohn, J. (登録日: 2024-07-02, 公開日: 2024-07-31, 最終更新日: 2025-09-03)

主引用文献

Gully, B.S.,Ferreira Fernandes, J.,Gunasinghe, S.D.,Vuong, M.T.,Lui, Y.,Rice, M.T.,Rashleigh, L.,Lay, C.S.,Littler, D.R.,Sharma, S.,Santos, A.M.,Venugopal, H.,Rossjohn, J.,Davis, S.J.
Structure of a fully assembled gamma delta T cell antigen receptor.
Nature, 634:729-736, 2024

PubMed Abstract: T cells in jawed vertebrates comprise two lineages, αβ T cells and γδ T cells, defined by the antigen receptors they express-that is, αβ and γδ T cell receptors (TCRs), respectively. The two lineages have different immunological roles, requiring that γδ TCRs recognize more structurally diverse ligands. Nevertheless, the receptors use shared CD3 subunits to initiate signalling. Whereas the structural organization of αβ TCRs is understood, the architecture of γδ TCRs is unknown. Here, we used cryogenic electron microscopy to determine the structure of a fully assembled, MR1-reactive, human Vγ8Vδ3 TCR-CD3δγεζ complex bound by anti-CD3ε antibody Fab fragments. The arrangement of CD3 subunits in γδ and αβ TCRs is conserved and, although the transmembrane α-helices of the TCR-γδ and -αβ subunits differ markedly in sequence, packing of the eight transmembrane-helix bundles is similar. However, in contrast to the apparently rigid αβ TCR, the γδ TCR exhibits considerable conformational heterogeneity owing to the ligand-binding TCR-γδ subunits being tethered to the CD3 subunits by their transmembrane regions only. Reducing this conformational heterogeneity by transfer of the Vγ8Vδ3 TCR variable domains to an αβ TCR enhanced receptor signalling, suggesting that γδ TCR organization reflects a compromise between efficient signalling and the ability to engage structurally diverse ligands. Our findings reveal the marked structural plasticity of the TCR on evolutionary timescales, and recast it as a highly versatile receptor capable of initiating signalling as either a rigid or flexible structure.

PubMed: 39146975
DOI: 10.1038/s41586-024-07920-0

実験手法

ELECTRON MICROSCOPY (3.01 Å)