ArticleJournal of molecular biology2021
Conformational Clamping by a Membrane Ligand Activates the EphA2 Receptor.
Article in Journal of molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Pooled it
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- [Npj imaging · 2026Article
- The Interaction between the Tyrosine Kinase Receptor EphA2 and RNF5: Structural Insights from anComputational and structural biotechnology journal · 2026Article
- Cholesterol-dependent dimerization and conformational dynamics of EphA2 receptors from coarse-grained and all-atom simulations.Structure (London, England : 1993) · 2025Article
- Simulation of Neurotrophin Receptor Transmembrane Helix Interactions Reveals Active States and Distinct Signaling Mechanisms.JACS Au · 2025Article
- Targeting the EphA2 pathway: could it be the way for bone sarcomas?Cell communication and signaling : CCS · 2024Review
- Transmembrane helix interactions regulate oligomerization of the receptor tyrosine kinase EphA2.The Journal of biological chemistry · 2024Article
- Article
- Transmembrane dimers of type 1 receptors sample alternate configurations: MD simulations using coarse grain Martini 3 versus AlphaFold2 Multimer.Structure (London, England : 1993) · 2023Article
- Spiers Memorial Lecture: Analysis andFaraday discussions · 2021Article
- Activation of the PDGF β Receptor by a Persistent Artificial Signal Peptide.Journal of molecular biology · 2021Article
- Structural and Functional Insights into the Transmembrane Domain Association of Eph Receptors.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The EphA2 receptor is a promising drug target for cancer treatment, since EphA2 activation can inhibit metastasis and tumor progression. It has been recently described that the TYPE7 peptide activates EphA2 using a novel mechanism that involves binding to the single transmembrane domain of the receptor. TYPE7 is a conditional transmembrane (TM) ligand, which only inserts into membranes at neutral pH in the presence of the TM region of EphA2. However, how membrane interactions can activate EphA2 is not known. We systematically altered the sequence of TYPE7 to identify the binding motif used to activate EphA2. With the resulting six peptides, we performed biophysical and cell migration assays that identified a new potent peptide variant. We also performed a mutational screen that determined the helical interface that mediates dimerization of the TM domain of EphA2 in cells. These results, together with molecular dynamic simulations, allowed to elucidate the molecular mechanism that TYPE7 uses to activate EphA2, where the membrane peptide acts as a molecular clamp that wraps around the TM dimer of the receptor. We propose that this binding mode stabilizes the active conformation of EphA2. Our data, additionally, provide clues into the properties that TM ligands need to have in order to achieve activation of membrane receptors.
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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 Socratic graph.