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Yorodumi- PDB-8u4l: Structure of the HER2/HER4/NRG1b Heterodimer Extracellular Domain -
+Open data
-Basic information
Entry | Database: PDB / ID: 8u4l | ||||||||||||
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Title | Structure of the HER2/HER4/NRG1b Heterodimer Extracellular Domain | ||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / TRANSFERASE / Receptor Tyrosine Kinase | ||||||||||||
Function / homology | Function and homology information ERBB3 signaling pathway / positive regulation of peptidyl-tyrosine autophosphorylation / sequestering of metal ion / establishment of planar polarity involved in nephron morphogenesis / ERBB4 signaling pathway / ERBB4-ERBB4 signaling pathway / olfactory bulb interneuron differentiation / central nervous system morphogenesis / ventricular cardiac muscle cell differentiation / positive regulation of striated muscle cell differentiation ...ERBB3 signaling pathway / positive regulation of peptidyl-tyrosine autophosphorylation / sequestering of metal ion / establishment of planar polarity involved in nephron morphogenesis / ERBB4 signaling pathway / ERBB4-ERBB4 signaling pathway / olfactory bulb interneuron differentiation / central nervous system morphogenesis / ventricular cardiac muscle cell differentiation / positive regulation of striated muscle cell differentiation / neuregulin receptor activity / negative regulation of secretion / cardiac muscle tissue regeneration / animal organ development / negative regulation of immature T cell proliferation in thymus / endocardial cell differentiation / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / mitochondrial fragmentation involved in apoptotic process / neural crest cell development / cardiac muscle cell myoblast differentiation / cell communication / GABA receptor binding / PI3K events in ERBB4 signaling / cardiac muscle cell differentiation / mammary gland epithelial cell differentiation / embryonic pattern specification / mammary gland development / chemorepellent activity / ventricular trabecula myocardium morphogenesis / regulation of microtubule-based process / positive regulation of protein localization to cell surface / ErbB-3 class receptor binding / semaphorin receptor complex / Sema4D induced cell migration and growth-cone collapse / regulation of postsynaptic neurotransmitter receptor internalization / motor neuron axon guidance / neurotransmitter receptor localization to postsynaptic specialization membrane / activation of transmembrane receptor protein tyrosine kinase activity / ERBB signaling pathway / neural crest cell migration / epidermal growth factor receptor activity / negative regulation of cardiac muscle cell apoptotic process / PLCG1 events in ERBB2 signaling / neuromuscular junction development / ERBB2-EGFR signaling pathway / epidermal growth factor receptor binding / ERBB2 Activates PTK6 Signaling / positive regulation of Rho protein signal transduction / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / enzyme-linked receptor protein signaling pathway / positive regulation of transcription by RNA polymerase I / transmembrane receptor protein tyrosine kinase activator activity / ERBB2-ERBB3 signaling pathway / protein tyrosine kinase activator activity / Signaling by ERBB4 / oligodendrocyte differentiation / ERBB2 Regulates Cell Motility / cell surface receptor signaling pathway via JAK-STAT / Long-term potentiation / semaphorin-plexin signaling pathway / PI3K events in ERBB2 signaling / positive regulation of cell adhesion / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / SHC1 events in ERBB4 signaling / GABA-ergic synapse / positive regulation of protein targeting to membrane / mammary gland alveolus development / cell fate commitment / regulation of angiogenesis / coreceptor activity / Schwann cell development / Nuclear signaling by ERBB4 / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of cardiac muscle cell proliferation / regulation of cell migration / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / cell surface receptor protein tyrosine kinase signaling pathway / synapse assembly / Downregulation of ERBB4 signaling / lactation / GRB2 events in ERBB2 signaling / myelination / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / Downregulation of ERBB2:ERBB3 signaling / activation of protein kinase B activity / transmembrane receptor protein tyrosine kinase activity Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.31 Å | ||||||||||||
Authors | Trenker, R. / Diwanji, D. / Bingham, T. / Verba, K.A. / Jura, N. | ||||||||||||
Funding support | Germany, United States, 3items
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Citation | Journal: To Be Published Title: Structure of the HER2/HER4/NRG1b Heterodimer Extracellular Domain Authors: Trenker, R. / Diwanji, D. / Bingham, T. / Verba, K.A. / Jura, N. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8u4l.cif.gz | 454.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8u4l.ent.gz | 384.3 KB | Display | PDB format |
PDBx/mmJSON format | 8u4l.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8u4l_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 8u4l_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8u4l_validation.xml.gz | 51.5 KB | Display | |
Data in CIF | 8u4l_validation.cif.gz | 78 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u4/8u4l ftp://data.pdbj.org/pub/pdb/validation_reports/u4/8u4l | HTTPS FTP |
-Related structure data
Related structure data | 41886MC 8u4iC 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
-Protein , 3 types, 3 molecules ABC
#1: Protein | Mass: 67909.648 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ERBB4, HER4 / Cell line (production host): EXPI293F / Production host: Homo sapiens (human) References: UniProt: Q15303, receptor protein-tyrosine kinase |
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#2: Protein | Mass: 66888.008 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ERBB2, HER2, MLN19, NEU, NGL / Cell line (production host): EXPI293F / Production host: Homo sapiens (human) References: UniProt: P04626, receptor protein-tyrosine kinase |
#3: Protein | Mass: 5890.792 Da / Num. of mol.: 1 / Fragment: EGF-like domain (UNP residues 177-236) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NRG1, GGF, HGL, HRGA, NDF, SMDF / Plasmid: pET32 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): Origami B (DE3) / References: UniProt: Q02297 |
-Sugars , 6 types, 13 molecules
#4: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source | ||||||
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#5: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source | ||||||
#6: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #7: Polysaccharide | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Sugar | |
-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: Ternary complex of HER2/HER4/NRG1b / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | ||||||||||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Specimen support | Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 900 nm |
Image recording | Electron dose: 45.8 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.31 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 289192 / Symmetry type: POINT |