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Open data
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Basic information
Entry | Database: PDB / ID: 8hgp | ||||||
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Title | The EREG-bound EGFR/HER2 ectodomain complex | ||||||
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![]() | MEMBRANE PROTEIN | ||||||
Function / homology | ![]() luteinizing hormone signaling pathway / ovarian cumulus expansion / ovulation / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / Inhibition of Signaling by Overexpressed EGFR / EGFR interacts with phospholipase C-gamma / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / PLCG1 events in ERBB2 signaling ...luteinizing hormone signaling pathway / ovarian cumulus expansion / ovulation / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / Inhibition of Signaling by Overexpressed EGFR / EGFR interacts with phospholipase C-gamma / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / PLCG1 events in ERBB2 signaling / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / primary follicle stage / ERBB2-EGFR signaling pathway / ERBB2 Activates PTK6 Signaling / female meiotic nuclear division / semaphorin receptor complex / Signaling by EGFR / transmembrane receptor protein tyrosine kinase activator activity / PI3K events in ERBB4 signaling / Signaling by ERBB4 / regulation of microtubule-based process / ErbB-3 class receptor binding / ERBB2 Regulates Cell Motility / positive regulation of innate immune response / Sema4D induced cell migration and growth-cone collapse / motor neuron axon guidance / PI3K events in ERBB2 signaling / mRNA transcription / oocyte maturation / neurotransmitter receptor localization to postsynaptic specialization membrane / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / positive regulation of Rho protein signal transduction / epidermal growth factor receptor binding / neuromuscular junction development / 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 / GAB1 signalosome / positive regulation of DNA replication / enzyme-linked receptor protein signaling pathway / ERBB2-ERBB3 signaling pathway / positive regulation of transcription by RNA polymerase I / oligodendrocyte differentiation / positive regulation of phosphorylation / semaphorin-plexin signaling pathway / positive regulation of cell division / cellular response to epidermal growth factor stimulus / Signaling by ERBB2 / keratinocyte proliferation / positive regulation of cell adhesion / SHC1 events in ERBB4 signaling / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / positive regulation of protein targeting to membrane / anatomical structure morphogenesis / Complex I biogenesis / positive regulation of protein kinase activity / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in ERBB2 signaling / transmembrane receptor protein tyrosine kinase activity / regulation of angiogenesis / neurogenesis / SHC1 events in ERBB2 signaling / Respiratory electron transport / coreceptor activity / regulation of ERK1 and ERK2 cascade / Schwann cell development / basal plasma membrane / Nuclear signaling by ERBB4 / positive regulation of epithelial cell proliferation / keratinocyte differentiation / cell surface receptor protein tyrosine kinase signaling pathway / myelination / phosphatidylinositol 3-kinase/protein kinase B signal transduction / Downregulation of ERBB2:ERBB3 signaling / Constitutive Signaling by Overexpressed ERBB2 / positive regulation of mitotic nuclear division / positive regulation of smooth muscle cell proliferation / EGFR downregulation / Signaling by ERBB2 TMD/JMD mutants / positive regulation of MAP kinase activity / : / clathrin-coated endocytic vesicle membrane / mitochondrial electron transport, NADH to ubiquinone / Signaling by ERBB2 ECD mutants / proton motive force-driven mitochondrial ATP synthesis / positive regulation of cytokine production / Signaling by ERBB2 KD Mutants / epidermal growth factor receptor signaling pathway / NADH dehydrogenase (ubiquinone) activity Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.53 Å | ||||||
![]() | Zhang, Z. / Bai, X. | ||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 221.3 KB | Display | ![]() |
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PDB format | ![]() | 175.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 34745MC ![]() 8hgoC ![]() 8hgsC 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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1 |
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Components
-Protein , 2 types, 2 molecules BA
#1: Protein | Mass: 82149.758 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P04626, receptor protein-tyrosine kinase |
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#2: Protein | Mass: 81075.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P00533, receptor protein-tyrosine kinase |
-Protein/peptide , 1 types, 1 molecules C
#3: Protein/peptide | Mass: 5578.410 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Sugars , 3 types, 4 molecules ![](data/chem/img/NAG.gif)
#4: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Type: oligosaccharide / Mass: 748.682 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source |
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#5: Polysaccharide | 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: Sugar |
-Details
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 |
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Sample preparation
Component | Name: EREG-bound EGFR/HER2 ectodomain complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 0.2 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / 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) |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.53 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 273388 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
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