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Yorodumi- EMDB-13427: Structure of a fully assembled T-cell receptor engaging a tumor-a... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-13427 | |||||||||||||||
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Title | Structure of a fully assembled T-cell receptor engaging a tumor-associated peptide-MHC I | |||||||||||||||
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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 | single particle reconstruction / cryo EM / Resolution: 3.08 Å | |||||||||||||||
Authors | Susac L / Thomas C / Tampe R | |||||||||||||||
Funding support | Germany, 4 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_13427.map.gz | 204.3 MB | EMDB map data format | |
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Header (meta data) | emd-13427-v30.xml emd-13427.xml | 19 KB 19 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_13427_fsc.xml | 13.3 KB | Display | FSC data file |
Images | emd_13427.png | 91.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13427 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13427 | HTTPS FTP |
-Related structure data
Related structure data | 7phrMC 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_13427.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
+Entire : Fully assembled T-cell receptor engaging a tumor-associated pepti...
+Supramolecule #1: Fully assembled T-cell receptor engaging a tumor-associated pepti...
+Macromolecule #1: T-cell receptor alpha chain
+Macromolecule #2: T-cell receptor beta chain
+Macromolecule #3: T-cell surface glycoprotein CD3 gamma chain
+Macromolecule #4: T-cell surface glycoprotein CD3 delta chain, green fluorescent protein
+Macromolecule #5: T-cell surface glycoprotein CD3 epsilon chain
+Macromolecule #6: HLA class I histocompatibility antigen, A alpha chain
+Macromolecule #7: Beta-2-microglobulin
+Macromolecule #8: Tumor-associated antigentic peptide gp100
+Macromolecule #9: T-cell surface glycoprotein CD3 zeta chain
+Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 61.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |