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- PDB-9nfc: Structure of the cross-HLA supertype antibody R302 bound to a cla... -
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Open data
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Basic information
Entry | Database: PDB / ID: 9nfc | |||||||||||||||||||||||||||
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Title | Structure of the cross-HLA supertype antibody R302 bound to a class I MHC presenting a divarasib-modified KRAS-G12C peptide on HLA-A*03 | |||||||||||||||||||||||||||
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![]() | PROTEIN BINDING / Antibody / Cancer-neoantigen / complex | |||||||||||||||||||||||||||
Function / homology | ![]() positive regulation of memory T cell activation / T cell mediated cytotoxicity directed against tumor cell target / TAP complex binding / response to mineralocorticoid / GMP binding / Golgi medial cisterna / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / forebrain astrocyte development / positive regulation of CD8-positive, alpha-beta T cell proliferation ...positive regulation of memory T cell activation / T cell mediated cytotoxicity directed against tumor cell target / TAP complex binding / response to mineralocorticoid / GMP binding / Golgi medial cisterna / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / forebrain astrocyte development / positive regulation of CD8-positive, alpha-beta T cell proliferation / LRR domain binding / regulation of synaptic transmission, GABAergic / negative regulation of epithelial cell differentiation / response to isolation stress / CD8 receptor binding / response to gravity / epithelial tube branching involved in lung morphogenesis / antigen processing and presentation of exogenous peptide antigen via MHC class I / type I pneumocyte differentiation / beta-2-microglobulin binding / Rac protein signal transduction / endoplasmic reticulum exit site / positive regulation of Rac protein signal transduction / TAP binding / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / myoblast proliferation / protection from natural killer cell mediated cytotoxicity / skeletal muscle cell differentiation / RAS signaling downstream of NF1 loss-of-function variants / RUNX3 regulates p14-ARF / positive regulation of glial cell proliferation / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / SOS-mediated signalling / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / cardiac muscle cell proliferation / Signalling to RAS / Activated NTRK2 signals through FRS2 and FRS3 / SHC-related events triggered by IGF1R / detection of bacterium / Estrogen-stimulated signaling through PRKCZ / glial cell proliferation / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / T cell receptor binding / SHC-mediated cascade:FGFR2 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR4 / Erythropoietin activates RAS / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Signaling by CSF3 (G-CSF) / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / protein-membrane adaptor activity / p38MAPK events / FRS-mediated FGFR1 signaling / Signaling by FGFR3 in disease / Tie2 Signaling / striated muscle cell differentiation / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / Signaling by FLT3 fusion proteins / FLT3 Signaling / Signaling by FGFR1 in disease / EGFR Transactivation by Gastrin / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / homeostasis of number of cells within a tissue / GRB2 events in ERBB2 signaling / Downstream signal transduction / Ras activation upon Ca2+ influx through NMDA receptor / Insulin receptor signalling cascade / SHC1 events in ERBB2 signaling / response to glucocorticoid / Constitutive Signaling by Overexpressed ERBB2 / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / negative regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / VEGFR2 mediated cell proliferation / transferrin transport / small monomeric GTPase / cellular response to iron ion / lumenal side of endoplasmic reticulum membrane / Endosomal/Vacuolar pathway / FCERI mediated MAPK activation / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / peptide antigen assembly with MHC class II protein complex Similarity search - Function | |||||||||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.58 Å | |||||||||||||||||||||||||||
![]() | Maso, L. | |||||||||||||||||||||||||||
Funding support | 1items
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![]() | ![]() Title: Engineered antibodies that stabilize drug-modified KRASG12C neoantigens enable selective and potent cross-HLA immunotherapy Authors: Maso, L. / Mosure, S.A. / Rodriguez-Aponte, S.A. / Pizzo, A. / Mensah, D.N. / Southard, M. / Sze, S. / Vash, B. / Hattori, T. / Rajak, E. / Koide, A. / Neel, B.G. / Koide, S. / Liu, W. / ...Authors: Maso, L. / Mosure, S.A. / Rodriguez-Aponte, S.A. / Pizzo, A. / Mensah, D.N. / Southard, M. / Sze, S. / Vash, B. / Hattori, T. / Rajak, E. / Koide, A. / Neel, B.G. / Koide, S. / Liu, W. / Toenjes, S.T. / DaSilva-Jardine, P. / Chopra, R. / Rader, C. / Stopfer, L.E. | |||||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 138.4 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 37.3 KB | Display | |
Data in CIF | ![]() | 54.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 49362MC ![]() 9nfbC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 35323.738 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 11892.291 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Antibody , 2 types, 2 molecules DE
#4: Antibody | Mass: 23972.529 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#5: Antibody | Mass: 24136.109 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein/peptide / Non-polymers , 2 types, 2 molecules C
#3: Protein/peptide | Mass: 889.094 Da / Num. of mol.: 1 / Mutation: G12C / Source method: obtained synthetically / Source: (synth.) ![]() |
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#6: Chemical | ChemComp-A1AWR / Mass: 624.073 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C29H34ClF4N7O2 / Feature type: SUBJECT OF INVESTIGATION |
-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Binary complex of Fab R302 with divarasib-conjugated KRAS G12C peptide (7-16) presented by class I MHC having HLA-A*03:01 Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Molecular weight | Value: 0.1 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 4.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R0.6/1 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: blot time 4 s blot force 5 |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 2700 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 47.42 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
EM software | Name: Leginon / Version: 3.6 / Category: image acquisition |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 2.58 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 144769 / Symmetry type: POINT |