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- EMDB-37929: T cell receptor delta 2 gamma 9 with TCRD TM domain chimera of TRAC -

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Basic information

Entry
Database: EMDB / ID: EMD-37929
TitleT cell receptor delta 2 gamma 9 with TCRD TM domain chimera of TRAC
Map data
Sample
  • Complex: T cell receptor delta 2 gamma 9 with TCRD TM domain change to TRAC TM domain
    • Protein or peptide: T-cell surface glycoprotein CD3 zeta chain
    • Protein or peptide: T-cell surface glycoprotein CD3 delta chain
    • Protein or peptide: T-cell surface glycoprotein CD3 epsilon chain
    • Protein or peptide: T-cell surface glycoprotein CD3 gamma chain
    • Protein or peptide: Signal peptide,flag tag,T cell receptor delta variable 2,T cell receptor delta constant,T cell receptor alpha chain constant,T cell receptor delta variable 2,T cell receptor delta constant,T cell receptor alpha chain constant
    • Protein or peptide: Signal peptide,flag tag,T cell receptor gamma variable 9,T cell receptor gamma constant 1,T cell receptor gamma variable 9,T cell receptor gamma constant 1
Keywordsimmune / receptor / IMMUNE SYSTEM
Function / homology
Function and homology information


MHC protein binding / 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 ...MHC protein binding / 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 / response to bacterium / 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 / peptide antigen binding / 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 / 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 / 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 / Immunoreceptor tyrosine-based activation motif ...: / : / 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 / : / T-cell receptor alpha chain, constant domain / Domain of unknown function (DUF1968) / 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
T cell receptor delta variable 2 / T cell receptor delta constant / T cell receptor alpha chain 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 / T cell receptor gamma variable 9
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsXin W / Huang B / Chi X / Liu Y / Xu M / Zhang Y / Li X / Su Q / Zhou Q
Funding support China, 1 items
OrganizationGrant numberCountry
National Science Foundation (NSF, China) 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 31, 2023-
Header (metadata) releaseMay 8, 2024-
Map releaseMay 8, 2024-
UpdateJun 19, 2024-
Current statusJun 19, 2024Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_37929.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
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AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 200 pix.
= 215.46 Å
1.08 Å/pix.
x 200 pix.
= 215.46 Å
1.08 Å/pix.
x 200 pix.
= 215.46 Å

Surface

Projections

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.0773 Å
Density
Contour LevelBy AUTHOR: 0.02
Minimum - Maximum-0.115006804 - 0.16481788
Average (Standard dev.)-0.0003554525 (±0.0037209354)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 215.45999 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_37929_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_37929_half_map_2.map
Projections & Slices
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Sample components

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Entire : T cell receptor delta 2 gamma 9 with TCRD TM domain change to TRA...

EntireName: T cell receptor delta 2 gamma 9 with TCRD TM domain change to TRAC TM domain
Components
  • Complex: T cell receptor delta 2 gamma 9 with TCRD TM domain change to TRAC TM domain
    • Protein or peptide: T-cell surface glycoprotein CD3 zeta chain
    • Protein or peptide: T-cell surface glycoprotein CD3 delta chain
    • Protein or peptide: T-cell surface glycoprotein CD3 epsilon chain
    • Protein or peptide: T-cell surface glycoprotein CD3 gamma chain
    • Protein or peptide: Signal peptide,flag tag,T cell receptor delta variable 2,T cell receptor delta constant,T cell receptor alpha chain constant,T cell receptor delta variable 2,T cell receptor delta constant,T cell receptor alpha chain constant
    • Protein or peptide: Signal peptide,flag tag,T cell receptor gamma variable 9,T cell receptor gamma constant 1,T cell receptor gamma variable 9,T cell receptor gamma constant 1

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Supramolecule #1: T cell receptor delta 2 gamma 9 with TCRD TM domain change to TRA...

SupramoleculeName: T cell receptor delta 2 gamma 9 with TCRD TM domain change to TRAC TM domain
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: T-cell surface glycoprotein CD3 zeta chain

MacromoleculeName: T-cell surface glycoprotein CD3 zeta chain / type: protein_or_peptide / ID: 1 / Details: 168-195: twin-Strep tag / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 21.809695 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKR RGRDPEMGGK PQRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT KDTYDALHMQ A LPPRAAAW ...String:
MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKR RGRDPEMGGK PQRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT KDTYDALHMQ A LPPRAAAW SHPQFEKGGG SGGGSGGSAW SHPQFEK

UniProtKB: T-cell surface glycoprotein CD3 zeta chain

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Macromolecule #2: T-cell surface glycoprotein CD3 delta chain

MacromoleculeName: T-cell surface glycoprotein CD3 delta chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 18.949537 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT LLSDITRLDL GKRILDPRGI YRCNGTDIYK DKESTVQVH YRMCQSCVEL DPATVAGIIV TDVIATLLLA LGVFCFAGHE TGRLSGAADT QALLRNDQVY QPLRDRDDAQ Y SHLGGNWA RNK

UniProtKB: T-cell surface glycoprotein CD3 delta chain

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Macromolecule #3: T-cell surface glycoprotein CD3 epsilon chain

MacromoleculeName: T-cell surface glycoprotein CD3 epsilon chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.174227 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MQSGTHWRVL GLCLLSVGVW GQDGNEEMGG ITQTPYKVSI SGTTVILTCP QYPGSEILWQ HNDKNIGGDE DDKNIGSDED HLSLKEFSE LEQSGYYVCY PRGSKPEDAN FYLYLRARVC ENCMEMDVMS VATIVIVDIC ITGGLLLLVY YWSKNRKAKA K PVTRGAGA ...String:
MQSGTHWRVL GLCLLSVGVW GQDGNEEMGG ITQTPYKVSI SGTTVILTCP QYPGSEILWQ HNDKNIGGDE DDKNIGSDED HLSLKEFSE LEQSGYYVCY PRGSKPEDAN FYLYLRARVC ENCMEMDVMS VATIVIVDIC ITGGLLLLVY YWSKNRKAKA K PVTRGAGA GGRQRGQNKE RPPPVPNPDY EPIRKGQRDL YSGLNQRRI

UniProtKB: T-cell surface glycoprotein CD3 epsilon chain

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Macromolecule #4: T-cell surface glycoprotein CD3 gamma chain

MacromoleculeName: T-cell surface glycoprotein CD3 gamma chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 20.493457 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MEQGKGLAVL ILAIILLQGT LAQSIKGNHL VKVYDYQEDG SVLLTCDAEA KNITWFKDGK MIGFLTEDKK KWNLGSNAKD PRGMYQCKG SQNKSKPLQV YYRMCQNCIE LNAATISGFL FAEIVSIFVL AVGVYFIAGQ DGVRQSRASD KQTLLPNDQL Y QPLKDRED DQYSHLQGNQ LRRN

UniProtKB: T-cell surface glycoprotein CD3 gamma chain

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Macromolecule #5: Signal peptide,flag tag,T cell receptor delta variable 2,T cell r...

MacromoleculeName: Signal peptide,flag tag,T cell receptor delta variable 2,T cell receptor delta constant,T cell receptor alpha chain constant,T cell receptor delta variable 2,T cell receptor delta constant,T ...Name: Signal peptide,flag tag,T cell receptor delta variable 2,T cell receptor delta constant,T cell receptor alpha chain constant,T cell receptor delta variable 2,T cell receptor delta constant,T cell receptor alpha chain constant
type: protein_or_peptide / ID: 5 / Details: TCRDV2 with TM domain change to TRAC TM domain. / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 34.560738 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDMRVPAQLL GLLLLWLSGA RCMDYKDDDD KGGSETGAIE LVPEHQTVPV SIGVPATLRC SMKGEAIGNY YINWYRKTQG NTMTFIYRE KDIYGPGFKD NFQGDIDIAK NLAVLKILAP SERDEGSYYC ACDTLGMGGE YTDKLIFGKG TRVTVEPRSQ P HTKPSVFV ...String:
MDMRVPAQLL GLLLLWLSGA RCMDYKDDDD KGGSETGAIE LVPEHQTVPV SIGVPATLRC SMKGEAIGNY YINWYRKTQG NTMTFIYRE KDIYGPGFKD NFQGDIDIAK NLAVLKILAP SERDEGSYYC ACDTLGMGGE YTDKLIFGKG TRVTVEPRSQ P HTKPSVFV MKNGTNVACL VKEFYPKDIR INLVSSKKIT EFDPAIVISP SGKYNAVKLG KYEDSNSVTC SVQHDNKTVH ST DFEVKTD STDHVKPKET ENTKQPSKSC HKPKAIVHTE KVNMMSLTVL GLRILLLKVA GFNLLMTLRL WSS

UniProtKB: T cell receptor delta variable 2, T cell receptor delta constant, T cell receptor alpha chain constant

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Macromolecule #6: Signal peptide,flag tag,T cell receptor gamma variable 9,T cell r...

MacromoleculeName: Signal peptide,flag tag,T cell receptor gamma variable 9,T cell receptor gamma constant 1,T cell receptor gamma variable 9,T cell receptor gamma constant 1
type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.406973 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDMRVPAQLL GLLLLWLSGA RCMDYKDDDD KGGSETGAGH LEQPQISSTK TLSKTARLEC VVSGITISAT SVYWYRERPG EVIQFLVSI SYDGTVRKES GIPSGKFEVD RIPETSTSTL TIHNVEKQDI ATYYCALWEA QQELGKKIKV FGPGTKLIIT D KQLDADVS ...String:
MDMRVPAQLL GLLLLWLSGA RCMDYKDDDD KGGSETGAGH LEQPQISSTK TLSKTARLEC VVSGITISAT SVYWYRERPG EVIQFLVSI SYDGTVRKES GIPSGKFEVD RIPETSTSTL TIHNVEKQDI ATYYCALWEA QQELGKKIKV FGPGTKLIIT D KQLDADVS PKPTIFLPSI AETKLQKAGT YLCLLEKFFP DVIKIHWQEK KSNTILGSQE GNTMKTNDTY MKFSWLTVPE KS LDKEHRC IVRHENNKNG VDQEIIFPPI KTDVITMDPK DNCSKDANDT LLLQLTNTSA YYMYLLLLLK SVVYFAIITC CLL RRTAFC CNGEKS

UniProtKB: T cell receptor gamma variable 9, T cell receptor gamma constant 1

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 275838
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: MAXIMUM LIKELIHOOD

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