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Yorodumi- EMDB-13427: Structure of a fully assembled T-cell receptor engaging a tumor-a... -
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Basic information
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| Title | Structure of a fully assembled T-cell receptor engaging a tumor-associated peptide-MHC I | |||||||||||||||
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Keywords | T-cell receptor / TCR / Major Histocompatibility Complex / MHC / Antigen / Adaptive Immunity / Cancer / Complex / IMMUNE SYSTEM | |||||||||||||||
| Function / homology | Function and homology informationregulation of lymphocyte apoptotic process / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / cis-Golgi network membrane / positive regulation of melanin biosynthetic process / T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / melanin biosynthetic process / positive regulation of T cell anergy / Fc-gamma receptor signaling pathway ...regulation of lymphocyte apoptotic process / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / cis-Golgi network membrane / positive regulation of melanin biosynthetic process / T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / melanin biosynthetic process / positive regulation of T cell anergy / Fc-gamma receptor signaling pathway / gamma-delta T cell activation / CD4-positive, alpha-beta T cell proliferation / negative thymic T cell selection / melanosome membrane / melanosome organization / multivesicular body, internal vesicle / 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 memory T cell activation / T cell mediated cytotoxicity directed against tumor cell target / TAP complex binding / Golgi medial cisterna / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / positive regulation of CD8-positive, alpha-beta T cell proliferation / positive regulation of cell-matrix adhesion / smoothened signaling pathway / T cell receptor complex / CD8 receptor binding / 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 / positive regulation of interleukin-4 production / beta-2-microglobulin binding / establishment or maintenance of cell polarity / dendrite development / endoplasmic reticulum exit site / Regulation of MITF-M-dependent genes involved in pigmentation / protein complex oligomerization / TAP binding / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / alpha-beta T cell activation / protection from natural killer cell mediated cytotoxicity / Generation of second messenger molecules / FCGR activation / immunological synapse / Co-inhibition by PD-1 / 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 / Role of phospholipids in phagocytosis / detection of bacterium / T cell receptor binding / T cell costimulation / positive regulation of T cell proliferation / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / FCGR3A-mediated IL10 synthesis / cell surface receptor protein tyrosine kinase signaling pathway / protein tyrosine kinase binding / negative regulation of receptor binding / T cell activation / early endosome lumen / bioluminescence / Nef mediated downregulation of MHC class I complex cell surface expression / cerebellum development / DAP12 interactions / transferrin transport / cellular response to iron ion / Endosomal/Vacuolar pathway / negative regulation of smoothened signaling pathway / generation of precursor metabolites and energy / lumenal side of endoplasmic reticulum membrane / FCGR3A-mediated phagocytosis / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / peptide antigen assembly with MHC class II protein complex / apoptotic signaling pathway / cellular response to iron(III) ion / MHC class II protein complex / negative regulation of forebrain neuron differentiation / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / clathrin-coated endocytic vesicle membrane / ER to Golgi transport vesicle membrane / calcium-mediated signaling / peptide antigen assembly with MHC class I protein complex / regulation of iron ion transport / regulation of erythrocyte differentiation / HFE-transferrin receptor complex / response to molecule of bacterial origin / MHC class I peptide loading complex / T cell mediated cytotoxicity / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of immune response / MHC class I protein complex Similarity search - Function | |||||||||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.08 Å | |||||||||||||||
Authors | Susac L / Thomas C | |||||||||||||||
| Funding support | Germany, 4 items
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Citation | Journal: Cell / Year: 2022Title: 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. | |||||||||||||||
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Structure visualization
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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 | 21.6 KB 21.6 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 | ||
| Filedesc metadata | emd-13427.cif.gz | 7.3 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13427 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13427 | HTTPS FTP |
-Validation report
| Summary document | emd_13427_validation.pdf.gz | 506.9 KB | Display | EMDB validaton report |
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| Full document | emd_13427_full_validation.pdf.gz | 506.7 KB | Display | |
| Data in XML | emd_13427_validation.xml.gz | 13.4 KB | Display | |
| Data in CIF | emd_13427_validation.cif.gz | 18.3 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13427 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13427 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 7phrMC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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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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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| 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
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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 |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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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 |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
Germany, 4 items
Citation



















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Processing
FIELD EMISSION GUN

