8JBV

Extracellular domain of gamma delta TCR

8JBV の概要

• エントリーDOI: 10.2210/pdb8jbv/pdb
• EMDBエントリー: 36147
• 分子名称: T cell receptor delta variable 1,T cell receptor delta constant, T cell receptor gamma variable 5,T cell receptor gamma constant 1 (2 entities in total)
• 機能のキーワード: receptor, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 144151.49

構造登録者

Xin, W.,Chi, X.,Huang, B.,Su, Q.,Zhou, Q. (登録日: 2023-05-09, 公開日: 2024-05-08, 最終更新日: 2025-07-23)

主引用文献

Xin, W.,Huang, B.,Chi, X.,Liu, Y.,Xu, M.,Zhang, Y.,Li, X.,Su, Q.,Zhou, Q.
Structures of human gamma delta T cell receptor-CD3 complex.
Nature, 630:222-229, 2024

PubMed Abstract: Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology. The γδ T cell receptor (TCR), which is generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex. The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy. Here we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes, revealing two distinct assembly mechanisms that depend on Vγ usage. The Vγ9Vδ2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRγ-TCRδ extracellular domain and connecting peptides. The length of the connecting peptides regulates the ligand association and T cell activation. A cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signalling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, whereby two protomers nestle back to back through the Vγ5 domains of the TCR extracellular domains. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vγ5Vδ1 TCR is essential for T cell activation. These findings reveal organizing principles of the γδ TCR-CD3 complex, providing insights into the unique properties of γδ TCR and facilitating immunotherapeutic interventions.

PubMed: 38657677
DOI: 10.1038/s41586-024-07439-4

実験手法

ELECTRON MICROSCOPY (3.02 Å)