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- EMDB-36147: Extracellular domain of gamma delta TCR -

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Basic information

Entry
Database: EMDB / ID: EMD-36147
TitleExtracellular domain of gamma delta TCR
Map data
Sample
  • Complex: Extracellular domain of gamma delta TCR
    • Protein or peptide: T cell receptor delta variable 1,T cell receptor delta constant
    • Protein or peptide: T cell receptor gamma variable 5,T cell receptor gamma constant 1
KeywordsReceptor / IMMUNE SYSTEM
Function / homology
Function and homology information


gamma-delta T cell receptor complex / gamma-delta T cell activation / T cell receptor complex / small molecule 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)
Methodsingle particle reconstruction / Resolution: 3.02 Å
AuthorsXin W / Chi X / Huang B / Su Q / Zhou Q
Funding support China, 1 items
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, 2023-
Header (metadata) releaseMay 8, 2024-
Map releaseMay 8, 2024-
UpdateMay 8, 2024-
Current statusMay 8, 2024Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_36147.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.087 Å
Density
Contour LevelBy AUTHOR: 0.521
Minimum - Maximum-3.5362146 - 5.488895
Average (Standard dev.)-0.0015925192 (±0.090098895)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 278.272 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_36147_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_36147_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Extracellular domain of gamma delta TCR

EntireName: Extracellular domain of gamma delta TCR
Components
  • Complex: Extracellular domain of gamma delta TCR
    • Protein or peptide: T cell receptor delta variable 1,T cell receptor delta constant
    • Protein or peptide: T cell receptor gamma variable 5,T cell receptor gamma constant 1

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Supramolecule #1: Extracellular domain of gamma delta TCR

SupramoleculeName: Extracellular domain of gamma delta TCR / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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

MacromoleculeName: T cell receptor delta variable 1,T cell receptor delta constant
type: protein_or_peptide / ID: 1
Details: Author stated: 1-22:Signal peptide, 23-31:Flag tag.
Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 34.320574 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDMRVPAQLL GLLLLWLSGA RCMDYKDDDD KGGSETGAQK VTQAQSSVSM PVRKAVTLNC LYETSWWSYY IFWYKQLPSK EMIFLIRQG SDEQNAKSGR YSVNFKKAAK SVALTISALQ LEDSAKYFCA LGDPGGLNTD KLIFGKGTRV TVEPRSQPHT K PSVFVMKN ...String:
MDMRVPAQLL GLLLLWLSGA RCMDYKDDDD KGGSETGAQK VTQAQSSVSM PVRKAVTLNC LYETSWWSYY IFWYKQLPSK EMIFLIRQG SDEQNAKSGR YSVNFKKAAK SVALTISALQ LEDSAKYFCA LGDPGGLNTD KLIFGKGTRV TVEPRSQPHT K PSVFVMKN GTNVACLVKE FYPKDIRINL VSSKKITEFD PAIVISPSGK YNAVKLGKYE DSNSVTCSVQ HDNKTVHSTD FE VKTDSTD HVKPKETENT KQPSKSCHKP KAIVHTEKVN MMSLTVLGLR MLFAKTVAVN FLLTAKLFFL

UniProtKB: T cell receptor delta variable 1, T cell receptor delta constant

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Macromolecule #2: T cell receptor gamma variable 5,T cell receptor gamma constant 1

MacromoleculeName: T cell receptor gamma variable 5,T cell receptor gamma constant 1
type: protein_or_peptide / ID: 2
Details: Author stated: 1-22:Signal peptide, 23-31:Flag tag.
Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.755172 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDMRVPAQLL GLLLLWLSGA RCMDYKDDDD KGGSETGSSN LEGGTKSVTR PTRSSAEITC DLTVINAFYI HWYLHQEGKA PQRLLYYDV SNSKDVLESG LSPGKYYTHT PRRWSWILIL RNLIENDSGV YYCATWDRGN PKTHYYKKLF GSGTTLVVTD K QLDADVSP ...String:
MDMRVPAQLL GLLLLWLSGA RCMDYKDDDD KGGSETGSSN LEGGTKSVTR PTRSSAEITC DLTVINAFYI HWYLHQEGKA PQRLLYYDV SNSKDVLESG LSPGKYYTHT PRRWSWILIL RNLIENDSGV YYCATWDRGN PKTHYYKKLF GSGTTLVVTD K QLDADVSP KPTIFLPSIA ETKLQKAGTY LCLLEKFFPD VIKIHWQEKK SNTILGSQEG NTMKTNDTYM KFSWLTVPEK SL DKEHRCI VRHENNKNGV DQEIIFPPIK TDVITMDPKD NCSKDANDTL LLQLTNTSAY YMYLLLLLKS VVYFAIITCC LLR RTAFCC NGEKS

UniProtKB: T cell receptor gamma variable 5, T cell receptor gamma constant 1

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Experimental details

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Structure determination

Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.02 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 567573
FSC plot (resolution estimation)

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