ArticlePLoS computational biology2014
Membrane interaction of bound ligands contributes to the negative binding cooperativity of the EGF receptor.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Computational design of synthetic receptors with programmable signalling activity for enhanced cancer T cell therapy.Nature biomedical engineering · 2026Article
- Active regulation of the epidermal growth factor receptor by the membrane bilayer.bioRxiv : the preprint server for biology · 2025Article
- EGFR does not directly interact with cortical actin: A SRRF'n'TIRF study.Biophysical journal · 2024Article
- EGFR trafficking: effect of dimerization, dynamics, and mutation.Frontiers in oncology · 2023Review
- Structural Insight and Development of EGFR Tyrosine Kinase Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Glycosylation promotes the cancer regulator EGFR-ErbB2 heterodimer formation - molecular dynamics study.Journal of molecular modeling · 2021Article
- Receptor tyrosine kinase activation: From the ligand perspective.Current opinion in cell biology · 2020Review
- More than the sum of the parts: Toward full-length receptor tyrosine kinase structures.IUBMB life · 2019Review
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- Review
- Article
- Molecular dynamics simulations of membrane proteins and their interactions: from nanoscale to mesoscale.Current opinion in structural biology · 2016Review
- Structures of the EphA2 Receptor at the Membrane: Role of Lipid Interactions.Structure (London, England : 1993) · 2016Article
- Mechanistic Insights into R776H Mediated Activation of Epidermal Growth Factor Receptor Kinase.Biochemistry · 2015Article
- N-Glycosylation as determinant of epidermal growth factor receptor conformation in membranes.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- The juxtamembrane regions of human receptor tyrosine kinases exhibit conserved interaction sites with anionic lipids.Scientific reports · 2015Article
- A structural perspective on the regulation of the epidermal growth factor receptor.Annual review of biochemistry · 2015Review
- Putting together structures of epidermal growth factor receptors.Current opinion in structural biology · 2014Review
- Antihistamine response: a dynamically refined function at the host-tick interface.Parasites & vectors · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epidermal growth factor receptor (EGFR) plays a key role in regulating cell proliferation, migration, and differentiation, and aberrant EGFR signaling is implicated in a variety of cancers. EGFR signaling is triggered by extracellular ligand binding, which promotes EGFR dimerization and activation. Ligand-binding measurements are consistent with a negatively cooperative model in which the ligand-binding affinity at either binding site in an EGFR dimer is weaker when the other site is occupied by a ligand. This cooperativity is widely believed to be central to the effects of ligand concentration on EGFR-mediated intracellular signaling. Although the extracellular portion of the human EGFR dimer has been resolved crystallographically, the crystal structures do not reveal the structural origin of this negative cooperativity, which has remained unclear. Here we report the results of molecular dynamics simulations suggesting that asymmetrical interactions of the two binding sites with the membrane may be responsible (perhaps along with other factors) for this negative cooperativity. In particular, in our simulations the extracellular domains of an EGFR dimer spontaneously lay down on the membrane in an orientation in which favorable membrane contacts were made with one of the bound ligands, but could not be made with the other. Similar interactions were observed when EGFR was glycosylated, as it is in vivo.
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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.