Vgamma5 Vdelta1 T cell receptor complexVgamma5 Vdelta1 T cell receptor complex

Structural highlights

8jcb is a 16 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 9.5Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CD3Z_HUMAN Defects in CD247 are the cause of immunodeficiency due to defect in CD3-zeta (CD3ZID) [MIM:610163. An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens.[1]

Function

CD3Z_HUMAN Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering.

Publication Abstract from PubMed

Gamma delta (gammadelta) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology(1-3). The gammadelta T cell receptor (TCR), generated by gammadelta T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex(2). The gammadelta TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy(4). Here, we report the structures of two prototypical human Vgamma9Vdelta2 and Vgamma5Vdelta1 TCR-CD3 complexes(5,6), unveiling two distinct assembly mechanisms that depend on Vgamma usage. The Vgamma9Vdelta2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRgamma/TCRdelta 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 Vgamma5Vdelta1 TCR-CD3 complex displays a dimeric architecture, where two protomers nestle back-to-back via their Vgamma5 domains of TCR ECDs. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vgamma5Vdelta1 TCR is essential for T cell activation. These findings reveal organizing principles of the gammadelta TCR-CD3 complex, providing insights into the gammadelta TCR unique properties and facilitating immunotherapeutic interventions.

Structures of human gammadelta T cell receptor-CD3 complex.,Xin W, Huang B, Chi X, Liu Y, Xu M, Zhang Y, Li X, Su Q, Zhou Q Nature. 2024 Apr 24. doi: 10.1038/s41586-024-07439-4. PMID:38657677[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Rieux-Laucat F, Hivroz C, Lim A, Mateo V, Pellier I, Selz F, Fischer A, Le Deist F. Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency. N Engl J Med. 2006 May 4;354(18):1913-21. PMID:16672702 doi:354/18/1913
  2. Xin W, Huang B, Chi X, Liu Y, Xu M, Zhang Y, Li X, Su Q, Zhou Q. Structures of human γδ T cell receptor-CD3 complex. Nature. 2024 Apr 24. PMID:38657677 doi:10.1038/s41586-024-07439-4

8jcb, resolution 9.50Å

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