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- PDB-8wxe: Vgamma5Vdelta1 EH TCR-CD3 complex -

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Basic information

Entry
Database: PDB / ID: 8wxe
TitleVgamma5Vdelta1 EH TCR-CD3 complex
Components
  • (Signal peptide,flag tag,T cell receptor ...) x 2
  • (T-cell surface glycoprotein CD3 ...) x 4
KeywordsIMMUNE 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
: / : / CD3 gamma/delta subunit, Ig-like domain / T-cell surface glycoprotein CD3 delta chain / T-cell surface glycoprotein CD3 zeta subunit / Ig-like domain on T-cell surface glycoprotein CD3 epsilon chain / CD3 protein, epsilon/gamma/delta subunit / T-cell surface glycoprotein CD3 zeta subunit/High affinity IgE receptor gamma subunit / T-cell surface glycoprotein CD3 zeta chain / : ...: / : / CD3 gamma/delta subunit, Ig-like domain / T-cell surface glycoprotein CD3 delta chain / T-cell surface glycoprotein CD3 zeta subunit / Ig-like domain on T-cell surface glycoprotein CD3 epsilon chain / CD3 protein, epsilon/gamma/delta subunit / T-cell surface glycoprotein CD3 zeta subunit/High affinity IgE receptor gamma subunit / T-cell surface glycoprotein CD3 zeta chain / : / Immunoreceptor tyrosine-based activation motif / Phosphorylated immunoreceptor signalling ITAM / ITAM motif mammalian type profile. / Immunoreceptor tyrosine-based activation motif / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
CHOLESTEROL / T cell receptor gamma variable 5 / T cell receptor delta variable 1 / T cell receptor delta constant / T-cell surface glycoprotein CD3 delta chain / T-cell surface glycoprotein CD3 epsilon chain / T-cell surface glycoprotein CD3 gamma chain / T cell receptor gamma constant 1 / T-cell surface glycoprotein CD3 zeta chain
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å
AuthorsXin, W. / Huang, B. / Chi, X. / Xu, M. / Zhang, Y. / Li, X. / Su, Q. / Zhou, Q.
Funding support China, 1items
OrganizationGrant numberCountry
National Science Foundation (NSF, China)32022037 China
CitationJournal: 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
DepositionOct 28, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0May 8, 2024Provider: repository / Type: Initial release
Revision 1.1Jun 19, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
a: T-cell surface glycoprotein CD3 zeta chain
b: T-cell surface glycoprotein CD3 zeta chain
d: T-cell surface glycoprotein CD3 delta chain
e: T-cell surface glycoprotein CD3 epsilon chain
f: T-cell surface glycoprotein CD3 epsilon chain
g: T-cell surface glycoprotein CD3 gamma chain
m: Signal peptide,flag tag,T cell receptor delta variable 1,T cell receptor delta constant
n: Signal peptide,flag tag,T cell receptor gamma variable 5,T cell receptor gamma constant 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)201,8209
Polymers201,4338
Non-polymers3871
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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T-cell surface glycoprotein CD3 ... , 4 types, 6 molecules abdefg

#1: Protein T-cell surface glycoprotein CD3 zeta chain / T-cell receptor T3 zeta chain


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 T-cell surface glycoprotein CD3 delta chain / T-cell receptor T3 delta chain


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 T-cell surface glycoprotein CD3 epsilon chain / T-cell surface antigen T3/Leu-4 epsilon chain


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 T-cell surface glycoprotein CD3 gamma chain / T-cell receptor T3 gamma chain


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 Signal peptide,flag tag,T cell receptor delta variable 1,T cell receptor delta constant


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
#6: Protein Signal peptide,flag tag,T cell receptor gamma variable 5,T cell receptor gamma constant 1


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

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Non-polymers , 1 types, 1 molecules

#7: Chemical ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H46O / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: 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
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 342095 / Symmetry type: POINT

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