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- EMDB-37914: T cell receptor delta 2 gamma 9 with F283A, F290A, and F291A -

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Basic information

Entry
Database: EMDB / ID: EMD-37914
TitleT cell receptor delta 2 gamma 9 with F283A, F290A, and F291A
Map data
Sample
  • Cell: T cell receptor delta 2 gamma 9 with F283A, F290A, F291A
    • 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
    • Protein or peptide: Signal peptide,flag tag,T cell receptor gamma variable 9,T cell receptor gamma constant 1
  • Ligand: CHOLESTEROL
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 / Fc-gamma receptor signaling pathway / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation ...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 / Fc-gamma receptor signaling pathway / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / negative thymic T cell selection / positive regulation of CD4-positive, alpha-beta T cell proliferation / positive regulation of protein localization to cell surface / alpha-beta T cell receptor complex / positive thymic T cell selection / signal complex assembly / Nef and signal transduction / positive regulation of cell-matrix adhesion / T cell receptor complex / smoothened signaling pathway / establishment or maintenance of cell polarity / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / dendrite development / small molecule binding / Generation of second messenger molecules / alpha-beta T cell activation / immunological synapse / FCGR activation / PD-1 signaling / positive regulation of interleukin-4 production / Role of phospholipids in phagocytosis / negative regulation of smoothened signaling pathway / positive regulation of calcium-mediated signaling / positive regulation of T cell proliferation / protein tyrosine kinase binding / T cell costimulation / positive regulation of interleukin-2 production / T cell receptor binding / cerebellum development / T cell activation / FCGR3A-mediated IL10 synthesis / calcium-mediated signaling / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / clathrin-coated endocytic vesicle membrane / Regulation of actin dynamics for phagocytic cup formation / SH3 domain binding / peptide antigen binding / cell surface receptor protein tyrosine kinase signaling pathway / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of peptidyl-tyrosine phosphorylation / cell-cell junction / positive regulation of type II interferon production / transmembrane signaling receptor activity / signaling receptor complex adaptor activity / Cargo recognition for clathrin-mediated endocytosis / protein transport / Downstream TCR signaling / protein complex oligomerization / Clathrin-mediated endocytosis / cell body / T cell receptor signaling pathway / protein-containing complex assembly / regulation of apoptotic process / dendritic spine / adaptive immune response / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / protein heterodimerization activity / 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 / T-cell surface glycoprotein CD3 zeta subunit/High affinity IgE receptor gamma subunit / T-cell surface glycoprotein CD3 zeta chain / Ig-like domain on T-cell surface glycoprotein CD3 epsilon chain / CD3 protein, epsilon/gamma/delta subunit / Immunoreceptor tyrosine-based activation motif / Phosphorylated immunoreceptor signalling ITAM / ITAM motif mammalian type profile. ...CD3 gamma/delta subunit, Ig-like domain / T-cell surface glycoprotein CD3 delta chain / T-cell surface glycoprotein CD3 zeta subunit / T-cell surface glycoprotein CD3 zeta subunit/High affinity IgE receptor gamma subunit / T-cell surface glycoprotein CD3 zeta chain / Ig-like domain on T-cell surface glycoprotein CD3 epsilon chain / CD3 protein, epsilon/gamma/delta subunit / 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
T cell receptor delta variable 2 / 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 / T cell receptor gamma variable 9
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.8 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)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), 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
DepositionOct 30, 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_37914.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.0773 Å
Density
Contour LevelBy AUTHOR: 0.008
Minimum - Maximum-0.045112092 - 0.06888401
Average (Standard dev.)-0.00013917516 (±0.0015569945)
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: #2

Fileemd_37914_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_37914_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

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Sample components

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Entire : T cell receptor delta 2 gamma 9 with F283A, F290A, F291A

EntireName: T cell receptor delta 2 gamma 9 with F283A, F290A, F291A
Components
  • Cell: T cell receptor delta 2 gamma 9 with F283A, F290A, F291A
    • 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
    • Protein or peptide: Signal peptide,flag tag,T cell receptor gamma variable 9,T cell receptor gamma constant 1
  • Ligand: CHOLESTEROL

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Supramolecule #1: T cell receptor delta 2 gamma 9 with F283A, F290A, F291A

SupramoleculeName: T cell receptor delta 2 gamma 9 with F283A, F290A, F291A
type: cell / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
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
type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 34.331457 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 GLRMLFAKTV AVNALLTAKL AAL

UniProtKB: T cell receptor delta variable 2, T cell receptor delta 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
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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Macromolecule #7: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 1 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL / Cholesterol

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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
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: 1.0 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: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 294780

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