ArticleThe Journal of biological chemistry2013
Carboxyl group footprinting mass spectrometry and molecular dynamics identify key interactions in the HER2-HER3 receptor tyrosine kinase interface.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Positive prognostic value of HER2-HER3 co-expression and p-mTOR in gastric cancer patients.BMC cancer · 2017Pooled it
- Laser-Induced Dimeric Photoproducts of Chlorpromazine: LC-MS Identification and Molecular Docking Evidence of Enhanced Anticancer Potential.International journal of molecular sciences · 2025Article
- ERBB2/ ERBB3-mutated S100/ SOX10-positive unclassified high-grade uterine sarcoma: first detailed description of a novel entity.Virchows Archiv : an international journal of pathology · 2024Article
- Trans-activating mutations of the pseudokinase ERBB3.Oncogene · 2024Article
- Impact of camel milk lactoferrin peptides against breast cancer cells:Frontiers in pharmacology · 2024Article
- Review
- Mechanisms of neratinib resistance inCancer drug resistance (Alhambra, Calif.) · 2022Review
- Co-occurring gain-of-function mutations in HER2 and HER3 modulate HER2/HER3 activation, oncogenesis, and HER2 inhibitor sensitivity.Cancer cell · 2021Article
- The Radiolabeled HER3 Targeting Molecules for Tumor Imaging.Iranian journal of pharmaceutical research : IJPR · 2021Review
- Gastric Cancer Harboring anOncoTargets and therapy · 2021Article
- A novel anti-HER2 antibody GB235 reverses Trastuzumab resistance in HER2-expressing tumor cells in vitro and in vivo.Scientific reports · 2020Article
- Review
- Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.Journal of the American Society for Mass Spectrometry · 2018Article
- A comprehensive review of heregulins, HER3, and HER4 as potential therapeutic targets in cancer.Oncotarget · 2017Review
- Orthogonal Mass Spectrometry-Based Footprinting for Epitope Mapping and Structural Characterization: The IL-6 Receptor upon Binding of Protein Therapeutics.Analytical chemistry · 2017Article
- Biophysical Evidence for Intrinsic Disorder in the C-terminal Tails of the Epidermal Growth Factor Receptor (EGFR) and HER3 Receptor Tyrosine Kinases.The Journal of biological chemistry · 2017Article
- Probing the Time Scale of FPOP (Fast Photochemical Oxidation of Proteins): Radical Reactions Extend Over Tens of Milliseconds.Journal of the American Society for Mass Spectrometry · 2016Article
- Isotope-Encoded Carboxyl Group Footprinting for Mass Spectrometry-Based Protein Conformational Studies.Journal of the American Society for Mass Spectrometry · 2016Article
- Mapping of Fab-1:VEGF Interface Using Carboxyl Group Footprinting Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2015Article
- A structural perspective on the regulation of the epidermal growth factor receptor.Annual review of biochemistry · 2015Review
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Authors and funding
6 authors.
Funding
Abstract
The HER2 receptor tyrosine kinase is a driver oncogene in many human cancers, including breast and gastric cancer. Under physiologic levels of expression, HER2 heterodimerizes with other members of the EGF receptor/HER/ErbB family, and the HER2-HER3 dimer forms one of the most potent oncogenic receptor pairs. Previous structural biology studies have individually crystallized the kinase domains of HER2 and HER3, but the HER2-HER3 kinase domain heterodimer structure has yet to be solved. Using a reconstituted membrane system to form HER2-HER3 kinase domain heterodimers and carboxyl group footprinting mass spectrometry, we observed that HER2 and HER3 kinase domains preferentially form asymmetric heterodimers with HER3 and HER2 monomers occupying the donor and acceptor kinase positions, respectively. Conformational changes in the HER2 activation loop, as measured by changes in carboxyl group labeling, required both dimerization and nucleotide binding but did not require activation loop phosphorylation at Tyr-877. Molecular dynamics simulations on HER2-HER3 kinase dimers identify specific inter- and intramolecular interactions and were in good agreement with MS measurements. Specifically, several intermolecular ionic interactions between HER2 Lys-716-HER3 Glu-909, HER2 Glu-717-HER3 Lys-907, and HER2 Asp-871-HER3 Arg-948 were identified by molecular dynamics. We also evaluated the effect of the cancer-associated mutations HER2 D769H/D769Y, HER3 E909G, and HER3 R948K (also numbered HER3 E928G and R967K) on kinase activity in the context of this new structural model. This study provides valuable insights into the EGF receptor/HER/ErbB kinase structure and interactions, which can guide the design of future therapies.
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Registered trials
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