- EMDB-45808: G115 gamma delta TCR/CD3 complex bound by OKT3 Fab -
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Entry
Database: EMDB / ID: EMD-45808
Title
G115 gamma delta TCR/CD3 complex bound by OKT3 Fab
Map data
Sample
Complex: G115 gamma delta TCR/CD3 complex bound by OKT3 Fab
Protein or peptide: OKT3 Fab heavy chain
Protein or peptide: OKT3 Fab light chain
Protein or peptide: G115 TCR delta chain
Protein or peptide: G115 TCR gamma chain
Protein or peptide: T-cell surface glycoprotein CD3 delta chain
Protein or peptide: T-cell surface glycoprotein CD3 epsilon chain
Protein or peptide: T-cell surface glycoprotein CD3 gamma chain
Protein or peptide: T-cell surface glycoprotein CD3 zeta chain
Ligand: CHOLESTEROL
Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywords
TCR / CD3 / gamma delta / Fab / OKT3 / immune receptor / T cell / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information
regulation of lymphocyte apoptotic process / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / T cell anergy / positive regulation of T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / gamma-delta T cell activation / CD4-positive, alpha-beta T cell proliferation / Fc-gamma receptor signaling pathway / negative thymic T cell selection ...regulation of lymphocyte apoptotic process / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / T cell anergy / positive regulation of T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / gamma-delta T cell activation / CD4-positive, alpha-beta T cell proliferation / Fc-gamma receptor signaling pathway / negative thymic T cell selection / positive regulation of CD4-positive, alpha-beta T cell proliferation / alpha-beta T cell receptor complex / positive thymic T cell selection / positive regulation of protein localization to cell surface / signal complex assembly / Nef and signal transduction / positive regulation of cell-matrix adhesion / T cell receptor complex / smoothened signaling pathway / establishment or maintenance of cell polarity / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / positive regulation of interleukin-4 production / dendrite development / protein complex oligomerization / alpha-beta T cell activation / Generation of second messenger molecules / FCGR activation / immunological synapse / Co-inhibition by PD-1 / Role of phospholipids in phagocytosis / T cell receptor binding / positive regulation of T cell proliferation / T cell costimulation / negative regulation of smoothened signaling pathway / positive regulation of interleukin-2 production / cerebellum development / positive regulation of calcium-mediated signaling / FCGR3A-mediated IL10 synthesis / protein tyrosine kinase binding / T cell activation / FCGR3A-mediated phagocytosis / apoptotic signaling pathway / clathrin-coated endocytic vesicle membrane / calcium-mediated signaling / Regulation of actin dynamics for phagocytic cup formation / SH3 domain binding / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of type II interferon production / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of peptidyl-tyrosine phosphorylation / transmembrane signaling receptor activity / Downstream TCR signaling / protein transport / cell-cell junction / Cargo recognition for clathrin-mediated endocytosis / signaling receptor complex adaptor activity / T cell receptor signaling pathway / Clathrin-mediated endocytosis / cell body / protein-containing complex assembly / regulation of apoptotic process / dendritic spine / adaptive immune response / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / protein heterodimerization activity / external side of plasma membrane / negative regulation of gene expression / positive regulation of gene expression / protein kinase binding / Golgi apparatus / endoplasmic reticulum / protein homodimerization activity / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function
Journal: Nat Commun / Year: 2025 Title: Structural characterization of two γδ TCR/CD3 complexes. Authors: Mohammed Hoque / John Benji Grigg / Trudy Ramlall / Jennifer Jones / Luke L McGoldrick / John C Lin / William C Olson / Eric Smith / Matthew C Franklin / Tong Zhang / Kei Saotome / Abstract: The T-cell receptor (TCR)/CD3 complex plays an essential role in the immune response and is a key player in cancer immunotherapies. There are two classes of TCR/CD3 complexes, defined by their TCR ...The T-cell receptor (TCR)/CD3 complex plays an essential role in the immune response and is a key player in cancer immunotherapies. There are two classes of TCR/CD3 complexes, defined by their TCR chain usage (αβ or γδ). Recently reported structures have revealed the organization of the αβ TCR/CD3 complex, but similar studies regarding the γδ TCR/CD3 complex have lagged behind. Here, we report cryoelectron microscopy (cryoEM) structural analysis of two γδ TCRs, G115 (Vγ9 Vδ2) and 9C2 (Vγ5 Vδ1), in complex with CD3 subunits. Our results show that the overall subunit organization of the γδ TCR/CD3 complexes is similar to αβ TCRs. However, both γδ TCRs display highly mobile extracellular domains (ECDs), unlike αβ TCRs, which have TCR ECDs that are rigidly coupled to its transmembrane (TM) domains. We corroborate this finding in cells by demonstrating that a γδ T-cell specific antibody can bind a site that would be inaccessible in the more rigid αβ TCR/CD3 complex. Furthermore, we observed that the Vγ5 Vδ1 complex forms a TCR γ5 chain-mediated dimeric species whereby two TCR/CD3 complexes are assembled. Collectively, these data shed light on γδ TCR/CD3 complex formation and may aid the design of γδ TCR-based therapies.
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