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- PDB-8jbv: Extracellular domain of gamma delta TCR -

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Basic information

Entry
Database: PDB / ID: 8jbv
TitleExtracellular domain of gamma delta TCR
Components
  • T cell receptor delta variable 1,T cell receptor delta constant
  • T cell receptor gamma variable 5,T cell receptor gamma constant 1
KeywordsIMMUNE SYSTEM / Receptor
Function / homology
Function and homology information


gamma-delta T cell receptor complex / gamma-delta T cell activation / T cell receptor complex / small molecule binding / peptide antigen binding / T cell receptor signaling pathway / adaptive immune response / immune response / external side of plasma membrane / innate immune response ...gamma-delta T cell receptor complex / gamma-delta T cell activation / T cell receptor complex / small molecule binding / peptide antigen binding / T cell receptor signaling pathway / adaptive immune response / immune response / external side of plasma membrane / innate immune response / extracellular space / plasma membrane
Similarity search - Function
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
T cell receptor gamma variable 5 / T cell receptor delta variable 1 / T cell receptor delta constant / T cell receptor gamma constant 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / Resolution: 3.02 Å
AuthorsXin, W. / Chi, X. / Huang, B. / Su, Q. / Zhou, Q.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) 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), 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
DepositionMay 9, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0May 8, 2024Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
m: T cell receptor delta variable 1,T cell receptor delta constant
n: T cell receptor gamma variable 5,T cell receptor gamma constant 1
M: T cell receptor delta variable 1,T cell receptor delta constant
N: T cell receptor gamma variable 5,T cell receptor gamma constant 1


Theoretical massNumber of molelcules
Total (without water)144,1514
Polymers144,1514
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein T cell receptor delta variable 1,T cell receptor delta constant


Mass: 34320.574 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: Author stated: 1-22:Signal peptide, 23-31:Flag tag.
Source: (gene. exp.) Homo sapiens (human) / Gene: TRDV1, TRDC / Production host: Homo sapiens (human) / References: UniProt: A0A1B0GX56, UniProt: B7Z8K6
#2: Protein T cell receptor gamma variable 5,T cell receptor gamma constant 1


Mass: 37755.172 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: Author stated: 1-22:Signal peptide, 23-31:Flag tag.
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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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: Extracellular domain of gamma delta TCR / Type: COMPLEX / Entity ID: all / 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: NO

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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 FIELDBright-field microscopy / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.14_3260: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.02 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 567573 / Symmetry type: POINT

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