+Open data
-Basic information
Entry | Database: PDB / ID: 8hgs | ||||||
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Title | The EGF-bound EGFR ectodomain homodimer | ||||||
Components |
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Keywords | MEMBRANE PROTEIN | ||||||
Function / homology | Function and homology information negative regulation of secretion / positive regulation of hyaluronan biosynthetic process / negative regulation of cholesterol efflux / positive regulation of cerebellar granule cell precursor proliferation / cerebellar granule cell precursor proliferation / positive regulation of epithelial tube formation / regulation of calcium ion import / positive regulation of protein localization to early endosome / regulation of protein localization to cell surface / positive regulation of ubiquitin-dependent protein catabolic process ...negative regulation of secretion / positive regulation of hyaluronan biosynthetic process / negative regulation of cholesterol efflux / positive regulation of cerebellar granule cell precursor proliferation / cerebellar granule cell precursor proliferation / positive regulation of epithelial tube formation / regulation of calcium ion import / positive regulation of protein localization to early endosome / regulation of protein localization to cell surface / positive regulation of ubiquitin-dependent protein catabolic process / response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / diterpenoid metabolic process / regulation of receptor signaling pathway via JAK-STAT / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / response to UV-A / epidermal growth factor binding / PLCG1 events in ERBB2 signaling / tongue development / NFE2L2 regulating tumorigenic genes / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / regulation of nitric-oxide synthase activity / epidermal growth factor receptor binding / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / branching morphogenesis of an epithelial tube / intracellular vesicle / Signaling by EGFR / response to cobalamin / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / Signaling by ERBB4 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / eyelid development in camera-type eye / protein insertion into membrane / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / positive regulation of receptor internalization / regulation of JNK cascade / : / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of mitotic cell cycle / hair follicle development / MAP kinase kinase kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / embryonic placenta development / mammary gland alveolus development / positive regulation of bone resorption / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of DNA binding / GAB1 signalosome / positive regulation of nitric oxide mediated signal transduction / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / regulation of peptidyl-tyrosine phosphorylation / positive regulation of phosphorylation / positive regulation of glial cell proliferation / positive regulation of vasoconstriction / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / positive regulation of endothelial cell proliferation / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / cellular response to cadmium ion / positive regulation of DNA repair / EGFR Transactivation by Gastrin / ERK1 and ERK2 cascade / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / SHC1 events in ERBB2 signaling / positive regulation of endothelial cell migration / ossification / positive regulation of mitotic nuclear division / positive regulation of synaptic transmission, glutamatergic / neurogenesis / cellular response to dexamethasone stimulus / guanyl-nucleotide exchange factor activity / basal plasma membrane / regulation of ERK1 and ERK2 cascade / neuron projection morphogenesis / positive regulation of superoxide anion generation / platelet alpha granule lumen / positive regulation of peptidyl-threonine phosphorylation / positive regulation of DNA replication / Signal transduction by L1 Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.81 Å | ||||||
Authors | Zhang, Z. / Bai, X. | ||||||
Funding support | China, 1items
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Citation | Journal: Cell Discov / Year: 2023 Title: Structure and dynamics of the EGFR/HER2 heterodimer. Authors: Xue Bai / Pengyu Sun / Xinghao Wang / Changkun Long / Shuyun Liao / Song Dang / Shangshang Zhuang / Yongtao Du / Xinyi Zhang / Nan Li / Kangmin He / Zhe Zhang / Abstract: HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly ...HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly through dimerization with other family members, such as EGFR. However, the molecular details for heterodimer assembly have not been completely understood. Here, we report cryo-EM structures of the EGF- and epiregulin-bound EGFR/HER2 ectodomain complexes at resolutions of 3.3 Å and 4.5 Å, respectively. Together with the functional analyses, we demonstrate that only the dimerization arm of HER2, but not that of EGFR, is essential for their heterodimer formation and signal transduction. Moreover, we analyze the differential membrane dynamics and transient interactions of endogenous EGFR and HER2 molecules in genome-edited cells using single-molecule live-cell imaging. Furthermore, we show that the interaction with HER2 could allow EGFR to resist endocytosis. Together, this work deepens our understanding of the unique structural properties and dynamics of the EGFR/HER2 complex. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8hgs.cif.gz | 313.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8hgs.ent.gz | 240.6 KB | Display | PDB format |
PDBx/mmJSON format | 8hgs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hg/8hgs ftp://data.pdbj.org/pub/pdb/validation_reports/hg/8hgs | HTTPS FTP |
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-Related structure data
Related structure data | 34746MC 8hgoC 8hgpC 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
#1: Protein | Mass: 81075.297 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR, ERBB, ERBB1, HER1 / Cell line (production host): HEK293S GnTI- / Production host: Homo sapiens (human) References: UniProt: P00533, receptor protein-tyrosine kinase #2: Protein | Mass: 6555.376 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EGF / Production host: Escherichia coli (E. coli) / References: UniProt: P01133 #3: Polysaccharide | Type: oligosaccharide / Mass: 748.682 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source #4: Sugar | ChemComp-NAG / Has ligand of interest | Y | |
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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: EGF-bound EGFR ectodomain homodimer / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Value: 0.2 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293S GnTI- |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 4.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1500 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60.8 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.81 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 196557 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
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