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IF	>30 >20 >10 >5 all

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Structure paper

タイトル	Structures of human γδ T cell receptor-CD3 complex.
ジャーナル・号・ページ	Nature, Year 2024
掲載日	2024年4月24日
著者	Weizhi Xin / Bangdong Huang / Ximin Chi / Yuehua Liu / Mengjiao Xu / Yuanyuan Zhang / Xu Li / Qiang Su / Qiang Zhou /
PubMed 要旨	Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology. The γδ T cell receptor (TCR), generated by γδ T cells, recognizes a diverse ...Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology. The γδ T cell receptor (TCR), 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, unveiling 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 (ECD) and connecting peptides (CPs). The length of CPs regulates the ligand association and T cell activation. Additionally, a cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signaling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, where two protomers nestle back-to-back via their Vγ5 domains of TCR ECDs. 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 γδ TCR unique properties and facilitating immunotherapeutic interventions.
リンク	Nature / PubMed:38657677
手法	EM (単粒子)
解像度	3.0 - 9.5 Å
構造データ	36147 8jbv EMDB-36147, PDB-8jbv: Extracellular domain of gamma delta TCR 手法: EM (単粒子) / 解像度: 3.02 Å 36149 8jc0 EMDB-36149, PDB-8jc0: V gamma9 V delta2 TCR and CD3 complex in LMNG 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-36152: Vgamma5 Vdelta1 TCR complex (MPDI/TMDI) 手法: EM (単粒子) / 解像度: 3.9 Å EMDB-36153: Vgamma5 Vdelta1 TCR complex (MPDII/TMDII) 手法: EM (単粒子) / 解像度: 3.9 Å EMDB-36155: Vgamma5 Vdelta1 TCR complex (MPD/TMD) 手法: EM (単粒子) / 解像度: 5.7 Å 36156 8jcb EMDB-36156, PDB-8jcb: Vgamma5 Vdelta1 T cell receptor complex 手法: EM (単粒子) / 解像度: 9.5 Å 37904 8wxe EMDB-37904, PDB-8wxe: Vgamma5Vdelta1 EH TCR-CD3 complex 手法: EM (単粒子) / 解像度: 4.0 Å 37914 8wy0 EMDB-37914, PDB-8wy0: T cell receptor delta 2 gamma 9 with F283A, F290A, and F291A 手法: EM (単粒子) / 解像度: 3.8 Å 37929 8wyi EMDB-37929, PDB-8wyi: T cell receptor delta 2 gamma 9 with TCRD TM domain chimera of TRAC 手法: EM (単粒子) / 解像度: 3.9 Å 39128 8yc0 EMDB-39128, PDB-8yc0: T cell receptor V delta2 V gamma9 in GDN 手法: EM (単粒子) / 解像度: 4.12 Å EMDB-39359: T cell receptor V delta2 V gamma9 in GDN (DeepEMhancer) 手法: EM (単粒子) / 解像度: 3.9 Å EMDB-39361: Vgamma5 Vdelta1 TCR complex (MPDI/TMDI, DeepEMhancer) 手法: EM (単粒子) / 解像度: 3.9 Å EMDB-39362: Vgamma5 Vdelta1 TCR complex (MPDII/TMDII, DeepEMhancer) 手法: EM (単粒子) / 解像度: 3.9 Å EMDB-39363: V gamma9 V delta2 TCR and CD3 complex in LMNG (DeepEMhancer) 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-39367: Vgamma5 Vdelta1 TCR-CD3 complex (EH mutant, DeepEMhancer) 手法: EM (単粒子) / 解像度: 4.0 Å EMDB-39368: Extracellular domain of Vgamma5 Vdelta1 TCR (DeepEMhancer) 手法: EM (単粒子) / 解像度: 3.0 Å
化合物	ChemComp-CLR: CHOLESTEROL / コレステロ-ル / コレステロール
由来	homo sapiens (ヒト)
キーワード	IMMUNE SYSTEM (免疫系) / Receptor / immunity / immune