+Open data
-Basic information
Entry | Database: PDB / ID: 8wxe | ||||||
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Title | Vgamma5Vdelta1 EH TCR-CD3 complex | ||||||
Components |
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Keywords | IMMUNE SYSTEM / immunity / receptor | ||||||
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 / Fc-gamma receptor signaling pathway / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / 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 / Fc-gamma receptor signaling pathway / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / negative thymic T cell selection / positive regulation of CD4-positive, alpha-beta T cell proliferation / positive regulation of protein localization to cell surface / alpha-beta T cell receptor complex / positive thymic T cell selection / 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 / dendrite development / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / small molecule binding / alpha-beta T cell activation / Generation of second messenger molecules / immunological synapse / FCGR activation / PD-1 signaling / positive regulation of interleukin-4 production / Role of phospholipids in phagocytosis / negative regulation of smoothened signaling pathway / positive regulation of calcium-mediated signaling / positive regulation of T cell proliferation / protein tyrosine kinase binding / T cell costimulation / positive regulation of interleukin-2 production / cerebellum development / T cell receptor binding / T cell activation / FCGR3A-mediated IL10 synthesis / calcium-mediated signaling / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / clathrin-coated endocytic vesicle membrane / Regulation of actin dynamics for phagocytic cup formation / SH3 domain binding / cell surface receptor protein tyrosine kinase signaling pathway / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of peptidyl-tyrosine phosphorylation / cell-cell junction / signaling receptor complex adaptor activity / positive regulation of type II interferon production / transmembrane signaling receptor activity / protein transport / Cargo recognition for clathrin-mediated endocytosis / Downstream TCR signaling / protein complex oligomerization / Clathrin-mediated endocytosis / cell body / T cell receptor signaling pathway / protein-containing complex assembly / regulation of apoptotic process / dendritic spine / adaptive immune response / cell surface receptor signaling pathway / immune response / G protein-coupled receptor signaling pathway / protein heterodimerization activity / external side of plasma membrane / negative regulation of gene expression / innate immune response / positive regulation of gene expression / protein kinase binding / Golgi apparatus / endoplasmic reticulum / protein homodimerization activity / extracellular space / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | ||||||
Authors | Xin, W. / Huang, B. / Chi, X. / Xu, M. / Zhang, Y. / Li, X. / Su, Q. / Zhou, Q. | ||||||
Funding support | China, 1items
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Citation | Journal: Nature / Year: 2024 Title: Structures of human γδ T cell receptor-CD3 complex. Authors: Weizhi Xin / Bangdong Huang / Ximin Chi / Yuehua Liu / Mengjiao Xu / Yuanyuan Zhang / Xu Li / Qiang Su / Qiang Zhou / 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), 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8wxe.cif.gz | 146.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8wxe.ent.gz | 100 KB | Display | PDB format |
PDBx/mmJSON format | 8wxe.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wx/8wxe ftp://data.pdbj.org/pub/pdb/validation_reports/wx/8wxe | HTTPS FTP |
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-Related structure data
Related structure data | 37904MC 8jbvC 8jc0C 8jcbC 8wy0C 8wyiC 8yc0C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-T-cell surface glycoprotein CD3 ... , 4 types, 6 molecules abdefg
#1: Protein | Mass: 21809.695 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: 165-167: linker 168-195: twin-Strep tag / Source: (gene. exp.) Homo sapiens (human) / Gene: CD247, CD3Z, T3Z, TCRZ / Production host: Homo sapiens (human) / References: UniProt: P20963 #2: Protein | | Mass: 18949.537 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3D, T3D / Production host: Homo sapiens (human) / References: UniProt: P04234 #3: Protein | Mass: 23174.227 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3E, T3E / Production host: Homo sapiens (human) / References: UniProt: P07766 #4: Protein | | Mass: 20493.457 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3G, T3G / Production host: Homo sapiens (human) / References: UniProt: P09693 |
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-Signal peptide,flag tag,T cell receptor ... , 2 types, 2 molecules mn
#5: Protein | Mass: 34320.574 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1-22: signal peptide, 23-31: Flag tag, 38-131: A0A1B0GX56, 155-307: B7Z8K6 Source: (gene. exp.) Homo sapiens (human) / Gene: TRDV1, TRDC / Production host: Homo sapiens (human) / References: UniProt: A0A1B0GX56, UniProt: B7Z8K6 |
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#6: Protein | Mass: 37702.062 Da / Num. of mol.: 1 / Mutation: Y106E,R120H Source method: isolated from a genetically manipulated source Details: 1-22: signal peptide, 23-31: Flag tag, 38-137: UniprotKB ID A0A0B4J1U4, 159-331: UniprotKB ID P0CF51 with Y106E and R120H Source: (gene. exp.) Homo sapiens (human) / Gene: TRGV5, TCRGV5, TRGC1, TCRGC1 / Production host: Homo sapiens (human) / References: UniProt: A0A0B4J1U4, UniProt: P0CF51 |
-Non-polymers , 1 types, 1 molecules
#7: Chemical | ChemComp-CLR / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: T cell receptor delta 1 gamma 5 EH mutant / Type: COMPLEX / Details: Y106E and R120H in TCR gamma 5 chain / Entity ID: #1-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 342095 / Symmetry type: POINT |