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Yorodumi- PDB-6ulr: Molecular basis for tumor infiltrating TCR recognition of hotspot... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6ulr | ||||||
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Title | Molecular basis for tumor infiltrating TCR recognition of hotspot KRAS-G12D mutation | ||||||
Components |
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Keywords | IMMUNE SYSTEM / HLA-C Neoantigen KRAS | ||||||
Function / homology | Function and homology information myoblast differentiation / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / RAS signaling downstream of NF1 loss-of-function variants / tertiary granule membrane / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling ...myoblast differentiation / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / RAS signaling downstream of NF1 loss-of-function variants / tertiary granule membrane / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / Signalling to RAS / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Estrogen-stimulated signaling through PRKCZ / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / Erythropoietin activates RAS / SHC-mediated cascade:FGFR1 / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / Signaling by FGFR3 in disease / FRS-mediated FGFR4 signaling / p38MAPK events / Tie2 Signaling / FRS-mediated FGFR1 signaling / Signaling by FGFR2 in disease / positive regulation of endothelial cell proliferation / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / Ras activation upon Ca2+ influx through NMDA receptor / Signaling by FGFR1 in disease / GRB2 events in ERBB2 signaling / CD209 (DC-SIGN) signaling / NCAM signaling for neurite out-growth / SHC1 events in ERBB2 signaling / Downstream signal transduction / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / small monomeric GTPase / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / G protein activity / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / VEGFR2 mediated cell proliferation / 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 / 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 / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / RAF activation / cellular response to iron(III) ion / Signaling by high-kinase activity BRAF mutants / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / Constitutive Signaling by EGFRvIII / negative regulation of forebrain neuron differentiation / MAP2K and MAPK activation / Signaling by ERBB2 ECD mutants / 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 / Signaling by ERBB2 KD Mutants / MHC class I peptide loading complex / Signaling by SCF-KIT / 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 / MHC class I protein complex / multicellular organismal-level iron ion homeostasis / negative regulation of neurogenesis / peptide antigen assembly with MHC class II protein complex / positive regulation of receptor-mediated endocytosis / MHC class II protein complex / cellular response to nicotine / Regulation of RAS by GAPs / positive regulation of T cell mediated cytotoxicity / specific granule lumen / RAS processing / recycling endosome membrane / Negative regulation of MAPK pathway Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.2 Å | ||||||
Authors | Sun, P.D. / Sim, M.J.W. | ||||||
Citation | Journal: Proc.Natl.Acad.Sci.USA / Year: 2020 Title: High-affinity oligoclonal TCRs define effective adoptive T cell therapy targeting mutant KRAS-G12D. Authors: Sim, M.J.W. / Lu, J. / Spencer, M. / Hopkins, F. / Tran, E. / Rosenberg, S.A. / Long, E.O. / Sun, P.D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6ulr.cif.gz | 347.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6ulr.ent.gz | 267.2 KB | Display | PDB format |
PDBx/mmJSON format | 6ulr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ul/6ulr ftp://data.pdbj.org/pub/pdb/validation_reports/ul/6ulr | HTTPS FTP |
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-Related structure data
Related structure data | 6uliC 6ulkC 6ulnC 6uonC 4nt6S 6avgS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Protein , 4 types, 4 molecules ABDE
#1: Protein | Mass: 31837.107 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-Cw, HLA-C / Production host: Escherichia coli (E. coli) / References: UniProt: C1K0Y1 |
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#2: Protein | Mass: 11748.160 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 |
#4: Protein | Mass: 22651.082 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
#5: Protein | Mass: 27493.381 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
-Protein/peptide / Non-polymers , 2 types, 26 molecules C
#3: Protein/peptide | Mass: 761.802 Da / Num. of mol.: 1 / Mutation: G12D / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01111 |
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#6: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.02 Å3/Da / Density % sol: 59.33 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: 22% PEG 3350, 0.1M MOPS pH 7.1 and 0.25M MgSO4 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Jun 22, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3.2→39.827 Å / Num. obs: 17905 / % possible obs: 95.9 % / Redundancy: 5.4 % / Biso Wilson estimate: 44.73 Å2 / Rmerge(I) obs: 0.174 / Net I/σ(I): 25 |
Reflection shell | Resolution: 3.2→3.4 Å / Rmerge(I) obs: 0.488 / Mean I/σ(I) obs: 9.3 / Num. unique obs: 874 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4NT6, 6AVG Resolution: 3.2→39.82 Å / SU ML: 0.4246 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 25.751 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 45.04 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.2→39.82 Å
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Refine LS restraints |
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LS refinement shell |
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