ArticleThe Journal of biological chemistry2017
Biophysical Evidence for Intrinsic Disorder in the C-terminal Tails of the Epidermal Growth Factor Receptor (EGFR) and HER3 Receptor Tyrosine Kinases.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Modulating pseudokinase conformation from the ATP-binding site.Structure (London, England : 1993) · 2026Article
- Structure Characterization of a Disordered Peptide Using In-Droplet Hydrogen/Deuterium Exchange Mass Spectrometry and Molecular Dynamics.ACS physical chemistry Au · 2025Article
- Protein disorder - function paradigm: Putative role in inflammation.Bioinformation · 2025Article
- Intact Transition Epitope Mapping-Force Interferences by Variable Extensions (ITEM-FIVE).Biomolecules · 2024Article
- The relative binding position of Nck and Grb2 adaptors impacts actin-based motility of Vaccinia virus.eLife · 2022Article
- Ligand-induced transmembrane conformational coupling in monomeric EGFR.Nature communications · 2022Article
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Intrinsically disordered proteins play diverse roles in cell signaling.Cell communication and signaling : CCS · 2022Review
- Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs.Biomolecules · 2021Review
- Review
- Seeing Keratinocyte Proteins through the Looking Glass of Intrinsic Disorder.International journal of molecular sciences · 2021Review
- Structural and dynamic characterization of the C-terminal tail of ErbB2: Disordered but not random.Biophysical journal · 2021Article
- Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma.International journal of molecular sciences · 2021Review
- Phosphorylation-Dependent Conformations of the Disordered Carboxyl-Terminus Domain in the Epidermal Growth Factor Receptor.The journal of physical chemistry letters · 2020Article
- In-cell structural dynamics of an EGF receptor during ligand-induced dimer-oligomer transition.European biophysics journal : EBJ · 2020Article
- The transition model of RTK activation: A quantitative framework for understanding RTK signaling and RTK modulator activity.Cytokine & growth factor reviews · 2019Review
- The Structural and Functional Diversity of Intrinsically Disordered Regions in Transmembrane Proteins.The Journal of membrane biology · 2019Review
- Tracking Higher Order Protein Structure by Hydrogen-Deuterium Exchange Mass Spectrometry.Protein and peptide letters · 2019Review
- Deep mutational analysis reveals functional trade-offs in the sequences of EGFR autophosphorylation sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The epidermal growth factor receptor (EGFR)/ErbB family of receptor tyrosine kinases includes oncogenes important in the progression of breast and other cancers, and they are targets for many drug development strategies. Each member of the ErbB family possesses a unique, structurally uncharacterized C-terminal tail that plays an important role in autophosphorylation and signal propagation. To determine whether these C-terminal tails are intrinsically disordered regions, we conducted a battery of biophysical experiments on the EGFR and HER3 tails. Using hydrogen/deuterium exchange mass spectrometry, we measured the conformational dynamics of intracellular half constructs and compared the tails with the ordered kinase domains. The C-terminal tails demonstrate more rapid deuterium exchange behavior when compared with the kinase domains. Next, we expressed and purified EGFR and HER3 tail-only constructs. Results from circular dichroism spectroscopy, size exclusion chromatography with multiangle light scattering, dynamic light scattering, analytical ultracentrifugation, and small angle X-ray scattering each provide evidence that the EGFR and HER3 C-terminal tails are intrinsically disordered with extended, non-globular structure in solution. The intrinsic disorder and extended conformation of these tails may be important for their function by increasing the capture radius and reducing the thermodynamic barriers for binding of downstream signaling proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.