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Yorodumi- PDB-7phr: Structure of a fully assembled T-cell receptor engaging a tumor-a... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7phr | |||||||||||||||
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Title | Structure of a fully assembled T-cell receptor engaging a tumor-associated peptide-MHC I | |||||||||||||||
Components |
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Keywords | IMMUNE SYSTEM / T-cell receptor / TCR / Major Histocompatibility Complex / MHC / Antigen / Adaptive Immunity / Cancer / Complex | |||||||||||||||
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 / cis-Golgi network membrane / positive regulation of melanin biosynthetic process / 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 ...regulation of lymphocyte apoptotic process / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / T cell anergy / cis-Golgi network membrane / positive regulation of melanin biosynthetic process / 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 / melanin biosynthetic process / negative thymic T cell selection / Fc-gamma receptor signaling pathway / melanosome membrane / Regulation of MITF-M-dependent genes involved in pigmentation / multivesicular body, internal vesicle / melanosome organization / multivesicular body membrane / 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 / signal complex assembly / Nef and signal transduction / positive regulation of cell-matrix adhesion / T cell mediated cytotoxicity directed against tumor cell target / positive regulation of memory T cell activation / T cell receptor complex / TAP complex binding / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / establishment or maintenance of cell polarity / smoothened signaling pathway / Golgi medial cisterna / positive regulation of CD8-positive, alpha-beta T cell proliferation / CD8 receptor binding / positive regulation of interleukin-4 production / dendrite development / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / antigen processing and presentation of exogenous peptide antigen via MHC class I / endoplasmic reticulum exit site / alpha-beta T cell activation / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / TAP binding / Generation of second messenger molecules / immunological synapse / FCGR activation / protection from natural killer cell mediated cytotoxicity / PD-1 signaling / Role of phospholipids in phagocytosis / beta-2-microglobulin binding / T cell receptor binding / detection of bacterium / negative regulation of smoothened signaling pathway / positive regulation of T cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of calcium-mediated signaling / T cell costimulation / T cell activation / positive regulation of interleukin-2 production / bioluminescence / FCGR3A-mediated IL10 synthesis / cerebellum development / protein tyrosine kinase binding / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / generation of precursor metabolites and energy / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / cellular response to iron ion / Endosomal/Vacuolar pathway / lumenal side of endoplasmic reticulum membrane / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / calcium-mediated signaling / cellular response to iron(III) ion / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / clathrin-coated endocytic vesicle membrane / 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 / antigen processing and presentation of endogenous peptide antigen via MHC class I / positive regulation of T cell cytokine production / Regulation of actin dynamics for phagocytic cup formation / MHC class I protein complex / multicellular organismal-level iron ion homeostasis / negative regulation of neurogenesis Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) Aequorea victoria (jellyfish) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.08 Å | |||||||||||||||
Authors | Susac, L. / Thomas, C. / Tampe, R. | |||||||||||||||
Funding support | Germany, 4items
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Citation | Journal: Cell / Year: 2022 Title: Structure of a fully assembled tumor-specific T cell receptor ligated by pMHC. Authors: Lukas Sušac / Mai T Vuong / Christoph Thomas / Sören von Bülow / Caitlin O'Brien-Ball / Ana Mafalda Santos / Ricardo A Fernandes / Gerhard Hummer / Robert Tampé / Simon J Davis / Abstract: The T cell receptor (TCR) expressed by T lymphocytes initiates protective immune responses to pathogens and tumors. To explore the structural basis of how TCR signaling is initiated when the ...The T cell receptor (TCR) expressed by T lymphocytes initiates protective immune responses to pathogens and tumors. To explore the structural basis of how TCR signaling is initiated when the receptor binds to peptide-loaded major histocompatibility complex (pMHC) molecules, we used cryogenic electron microscopy to determine the structure of a tumor-reactive TCRαβ/CD3δγεζ complex bound to a melanoma-specific human class I pMHC at 3.08 Å resolution. The antigen-bound complex comprises 11 subunits stabilized by multivalent interactions across three structural layers, with clustered membrane-proximal cystines stabilizing the CD3-εδ and CD3-εγ heterodimers. Extra density sandwiched between transmembrane helices reveals the involvement of sterol lipids in TCR assembly. The geometry of the pMHC/TCR complex suggests that efficient TCR scanning of pMHC requires accurate pre-positioning of T cell and antigen-presenting cell membranes. Comparisons of the ligand-bound and unliganded receptors, along with molecular dynamics simulations, indicate that TCRs can be triggered in the absence of spontaneous structural rearrangements. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7phr.cif.gz | 268.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7phr.ent.gz | 214.4 KB | Display | PDB format |
PDBx/mmJSON format | 7phr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ph/7phr ftp://data.pdbj.org/pub/pdb/validation_reports/ph/7phr | HTTPS FTP |
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-Related structure data
Related structure data | 13427MC 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
-T-cell receptor ... , 2 types, 2 molecules AB
#1: Protein | Mass: 27979.268 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster) |
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#2: Protein | Mass: 32750.736 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster) |
-T-cell surface glycoprotein CD3 ... , 4 types, 6 molecules CDEeZz
#3: Protein | Mass: 13713.741 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3G, T3G / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P09693 | ||
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#4: Protein | Mass: 39858.188 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Aequorea victoria (jellyfish) Gene: CD3D, T3D, GFP / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P04234, UniProt: P42212 | ||
#5: Protein | Mass: 15316.222 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3E, T3E / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P07766 #9: Protein/peptide | Mass: 4138.015 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: Cricetulus griseus (Chinese hamster) / References: UniProt: P20963 |
-Protein , 2 types, 2 molecules HL
#6: Protein | Mass: 35054.613 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-A, HLAA / Production host: Escherichia coli (E. coli) / References: UniProt: P04439 |
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#7: Protein | Mass: 11936.408 Da / Num. of mol.: 1 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 |
-Protein/peptide / Sugars , 2 types, 7 molecules P
#10: Sugar | ChemComp-NAG / #8: Protein/peptide | | Mass: 974.107 Da / Num. of mol.: 1 / Mutation: A9V / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P40967 |
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-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: Fully assembled T-cell receptor engaging a tumor-associated peptide-MHC I Type: COMPLEX / Entity ID: #1-#9 / Source: MULTIPLE SOURCES | ||||||||||||
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||
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 |
Image recording | Electron dose: 61 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.08 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 154408 / Symmetry type: POINT | ||||||||||||||||||||||||
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