+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-39128 | |||||||||
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Title | T cell receptor V delta2 V gamma9 in GDN | |||||||||
Map data | ||||||||||
Sample |
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Keywords | 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 | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.12 Å | |||||||||
Authors | Xin W / Huang B / Chi X / Xu M / Zhang Y / Li X / Su Q / Zhou Q | |||||||||
Funding support | China, 1 items
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Citation | Journal: 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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_39128.map.gz | 27.6 MB | EMDB map data format | |
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Header (meta data) | emd-39128-v30.xml emd-39128.xml | 20.4 KB 20.4 KB | Display Display | EMDB header |
Images | emd_39128.png | 43.2 KB | ||
Filedesc metadata | emd-39128.cif.gz | 6.3 KB | ||
Others | emd_39128_half_map_1.map.gz emd_39128_half_map_2.map.gz | 23.3 MB 23.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-39128 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-39128 | HTTPS FTP |
-Related structure data
Related structure data | 8yc0MC 8jbvC 8jc0C 8jcbC 8wxeC 8wy0C 8wyiC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_39128.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_39128_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_39128_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : TCR V delta2 V gamma 9 in complex with CD3 in GDN
Entire | Name: TCR V delta2 V gamma 9 in complex with CD3 in GDN |
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Components |
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-Supramolecule #1: TCR V delta2 V gamma 9 in complex with CD3 in GDN
Supramolecule | Name: TCR V delta2 V gamma 9 in complex with CD3 in GDN / type: cell / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: T-cell surface glycoprotein CD3 zeta chain
Macromolecule | Name: T-cell surface glycoprotein CD3 zeta chain / type: protein_or_peptide / ID: 1 / Details: 168-195: step tag / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 21.809695 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 |
-Macromolecule #2: T-cell surface glycoprotein CD3 delta chain
Macromolecule | Name: T-cell surface glycoprotein CD3 delta chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 18.949537 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 |
-Macromolecule #3: T-cell surface glycoprotein CD3 epsilon chain
Macromolecule | Name: T-cell surface glycoprotein CD3 epsilon chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.174227 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 |
-Macromolecule #4: T-cell surface glycoprotein CD3 gamma chain
Macromolecule | Name: T-cell surface glycoprotein CD3 gamma chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 20.493457 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 |
-Macromolecule #5: T cell receptor delta variable 2,T cell receptor delta constant
Macromolecule | Name: T cell receptor delta variable 2,T cell receptor delta constant type: protein_or_peptide / ID: 5 / Details: 1-22: signal peptide 23-31: flag tag / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 34.559738 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 AVNFLLTAKL FFL UniProtKB: T cell receptor delta variable 2, T cell receptor delta constant |
-Macromolecule #6: T cell receptor gamma variable 9,T cell receptor gamma constant 1
Macromolecule | Name: T cell receptor gamma variable 9,T cell receptor gamma constant 1 type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.406973 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 |
-Macromolecule #7: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 1 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Image recording | Film 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 |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.12 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 119724 |