EMD-36156

Single-particle
9.5 Å
EMD-36156 Deposition: 10/05/2023
Map released: 08/05/2024
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-36156

Vgamma5 Vdelta1 T cell receptor complex

EMD-36156

Single-particle
9.5 Å
EMD-36156 Deposition: 10/05/2023
Map released: 08/05/2024
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Vgamma5 Vdelta1 T cell receptor complex
Fitted models: 8jcb (Avg. Q-score: 0.064)

Deposition Authors: Xin W , Huang B, Chi X, Xu M, Zhang Y, Li X , Su Q , Zhou Q
Structures of human gamma delta T cell receptor-CD3 complex.
Xin W , Huang B, Chi X, Liu Y, Xu M, Zhang Y, Li X , Su Q , Zhou Q
(2024) Nature , 630 , 222 - 229
PUBMED: 38657677
DOI: doi:10.1038/s41586-024-07439-4
ISSN: 1476-4687
ASTM: NATUAS
Abstract:
Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology1-3. The γδ T cell receptor (TCR), which is generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex2. The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy4. Here we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes5,6, 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.