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Yorodumi- PDB-8es9: CryoEM structure of PN45428 TCR-CD3 in complex with HLA-A2 MAGEA4 -
+Open data
-Basic information
Entry | Database: PDB / ID: 8es9 | ||||||
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Title | CryoEM structure of PN45428 TCR-CD3 in complex with HLA-A2 MAGEA4 | ||||||
Components |
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Keywords | IMMUNE SYSTEM / TCR / receptor / membrane protein / CD3 / MHC / HLA | ||||||
Function / homology | Function and homology information 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 / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / Fc-gamma receptor signaling pathway / negative thymic T cell selection ...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 / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / 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 regulation of protein localization to cell surface / positive thymic T cell selection / Nef and signal transduction / signal complex assembly / positive regulation of cell-matrix adhesion / T cell receptor complex / establishment or maintenance of cell polarity / smoothened signaling pathway / 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 / FCGR activation / Generation of second messenger molecules / immunological synapse / PD-1 signaling / positive regulation of cell cycle / Role of phospholipids in phagocytosis / T cell receptor binding / positive regulation of T cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / negative regulation of smoothened signaling pathway / T cell costimulation / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / protein complex oligomerization / protein tyrosine kinase binding / FCGR3A-mediated IL10 synthesis / cerebellum development / T cell activation / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / negative regulation of receptor binding / DAP12 interactions / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / cellular response to iron ion / Endosomal/Vacuolar pathway / apoptotic signaling pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / FCGR3A-mediated phagocytosis / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / cellular response to iron(III) ion / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / negative regulation of forebrain neuron differentiation / regulation of erythrocyte differentiation / peptide antigen assembly with MHC class I protein complex / ER to Golgi transport vesicle membrane / regulation of iron ion transport / response to molecule of bacterial origin / MHC class I peptide loading complex / HFE-transferrin receptor complex / T cell mediated cytotoxicity / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / sensory perception of smell / Regulation of actin dynamics for phagocytic cup formation / MHC class I protein complex / SH3 domain binding / histone deacetylase binding / negative regulation of neurogenesis / positive regulation of receptor-mediated endocytosis / peptide antigen assembly with MHC class II protein complex / multicellular organismal-level iron ion homeostasis / MHC class II protein complex / cellular response to nicotine / specific granule lumen / positive regulation of T cell mediated cytotoxicity / positive regulation of cellular senescence / positive regulation of type II interferon production / recycling endosome membrane / phagocytic vesicle membrane / positive regulation of peptidyl-tyrosine phosphorylation / peptide antigen binding / antigen processing and presentation of exogenous peptide antigen via MHC class II / negative regulation of epithelial cell proliferation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of immune response / Interferon gamma signaling / transmembrane signaling receptor activity / positive regulation of T cell activation / cell-cell junction Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.25 Å | ||||||
Authors | Saotome, K. / Franklin, M.C. | ||||||
Funding support | 1items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM. Authors: Kei Saotome / Drew Dudgeon / Kiersten Colotti / Michael J Moore / Jennifer Jones / Yi Zhou / Ashique Rafique / George D Yancopoulos / Andrew J Murphy / John C Lin / William C Olson / Matthew C Franklin / Abstract: The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity ...The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development of therapeutics. Despite the rapid rise of single particle cryoelectron microscopy (cryoEM), x-ray crystallography has remained the preferred method for structure determination of TCR-pMHC complexes. Here, we report cryoEM structures of two distinct full-length α/β TCR-CD3 complexes bound to their pMHC ligand, the cancer-testis antigen HLA-A2/MAGEA4 (230-239). We also determined cryoEM structures of pMHCs containing MAGEA4 (230-239) peptide and the closely related MAGEA8 (232-241) peptide in the absence of TCR, which provided a structural explanation for the MAGEA4 preference displayed by the TCRs. These findings provide insights into the TCR recognition of a clinically relevant cancer antigen and demonstrate the utility of cryoEM for high-resolution structural analysis of TCR-pMHC interactions. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8es9.cif.gz | 321.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8es9.ent.gz | 237.5 KB | Display | PDB format |
PDBx/mmJSON format | 8es9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8es9_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8es9_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8es9_validation.xml.gz | 55.5 KB | Display | |
Data in CIF | 8es9_validation.cif.gz | 80.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/es/8es9 ftp://data.pdbj.org/pub/pdb/validation_reports/es/8es9 | HTTPS FTP |
-Related structure data
Related structure data | 28572MC 8es7C 8es8C 8esaC 8esbC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 4 types, 4 molecules ABNM
#1: Protein | Mass: 30415.229 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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#2: Protein | Mass: 35487.352 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#7: Protein | Mass: 32082.512 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-A*02:01 / Production host: Escherichia coli (E. coli) / References: UniProt: Q861F7 |
#8: Protein | Mass: 11879.356 Da / Num. of mol.: 1 / Fragment: UNP residues 21-119 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: B2M, CDABP0092, HDCMA22P / Production host: Escherichia coli (E. coli) / References: UniProt: P61769 |
-T-cell surface glycoprotein CD3 ... , 4 types, 6 molecules ZYDFEG
#3: Protein | Mass: 19654.486 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD247, CD3Z, T3Z, TCRZ / Production host: Homo sapiens (human) / References: UniProt: P20963 #4: Protein | | Mass: 19150.719 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3D, T3D / Production host: Homo sapiens (human) / References: UniProt: P04234 #5: Protein | Mass: 23432.459 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3E, T3E / Production host: Homo sapiens (human) / References: UniProt: P07766 #6: Protein | | Mass: 20694.639 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3G, T3G / Production host: Homo sapiens (human) / References: UniProt: P09693 |
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-Protein/peptide / Non-polymers , 2 types, 2 molecules P
#13: Chemical | ChemComp-Y01 / |
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#9: Protein/peptide | Mass: 1134.200 Da / Num. of mol.: 1 / Fragment: peptide (UNP residues 230-239) / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P43358 |
-Sugars , 3 types, 9 molecules
#10: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source | ||
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#11: Polysaccharide | Source method: isolated from a genetically manipulated source #12: Sugar | ChemComp-NAG / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: PN45428 TCR-CD3 complex bound to HLA-A2 MAGEA4 (230-239) in the presence of 2M2 Fab Type: COMPLEX / Entity ID: #1-#9 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1400 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.25 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 107308 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 85.59 Å2 | ||||||||||||||||||||||||
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