+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 / 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 / Nef and signal transduction / signal complex assembly / positive regulation of cell-matrix adhesion / T cell receptor complex / smoothened signaling pathway / establishment or maintenance of cell polarity / small molecule binding / positive regulation of interleukin-4 production / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / dendrite development / alpha-beta T cell activation / protein complex oligomerization / FCGR activation / Generation of second messenger molecules / immunological synapse / PD-1 signaling / Role of phospholipids in phagocytosis / T cell receptor binding / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of T cell proliferation / negative regulation of smoothened signaling pathway / T cell costimulation / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / protein tyrosine kinase binding / FCGR3A-mediated IL10 synthesis / cerebellum development / T cell activation / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / Regulation of actin dynamics for phagocytic cup formation / SH3 domain binding / positive regulation of type II interferon production / positive regulation of peptidyl-tyrosine phosphorylation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / transmembrane signaling receptor activity / cell-cell junction / protein transport / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / signaling receptor complex adaptor activity / Clathrin-mediated endocytosis / T cell receptor signaling pathway / cell body / protein-containing complex assembly / regulation of apoptotic process / adaptive immune response / dendritic spine / cell surface receptor signaling pathway / immune response / protein heterodimerization activity / G protein-coupled receptor signaling pathway / 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), which is generated by γδ T cells, recognizes a ...Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology. The γδ T cell receptor (TCR), which is 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, 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. | ||||||
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 | 146.4 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
Summary document | 8wxe_validation.pdf.gz | 493.5 KB | Display | wwPDB validaton report |
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Full document | 8wxe_full_validation.pdf.gz | 495.3 KB | Display | |
Data in XML | 8wxe_validation.xml.gz | 11.1 KB | Display | |
Data in CIF | 8wxe_validation.cif.gz | 17.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wx/8wxe ftp://data.pdbj.org/pub/pdb/validation_reports/wx/8wxe | HTTPS FTP |
-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 FIELD / 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 |