ArticleBiochemistry2014
Dimerization of the EphA1 receptor tyrosine kinase transmembrane domain: Insights into the mechanism of receptor activation.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Membrane Protein Folding and Biogenesis: Insights from Single-Molecule Force Spectroscopy.Chemical reviews · 2026Review
- Molecular Insights into the Neurogenic Potential of Alpha-lipoic Acid.Current topics in medicinal chemistry · 2026Article
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- The Influence of Phosphoinositide Lipids in the Molecular Biology of Membrane Proteins: Recent Insights from Simulations.Journal of molecular biology · 2025Review
- Structural basis of dimerization of chemokine receptors CCR5 and CXCR4.Nature communications · 2023Article
- The role of structural heterogeneity in the homodimerization of transmembrane proteins.The Journal of chemical physics · 2023Article
- Transmembrane dimers of type 1 receptors sample alternate configurations: MD simulations using coarse grain Martini 3 versus AlphaFold2 Multimer.Structure (London, England : 1993) · 2023Article
- On Computing Equilibrium Binding Constants for Protein-Protein Association in Membranes.Journal of chemical theory and computation · 2022Article
- Modulation of adenosine A2a receptor oligomerization by receptor activation and PIPStructure (London, England : 1993) · 2021Article
- Structural and Functional Insights into the Transmembrane Domain Association of Eph Receptors.International journal of molecular sciences · 2021Review
- Addressing the Excessive Aggregation of Membrane Proteins in the MARTINI Model.Journal of chemical theory and computation · 2021Article
- The metastable states of proteins.Protein science : a publication of the Protein Society · 2020Review
- Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- The CD28 Transmembrane Domain Contains an Essential Dimerization Motif.Frontiers in immunology · 2020Article
- The Role of the Small Export Apparatus Protein, SctS, in the Activity of the Type III Secretion System.Frontiers in microbiology · 2019Article
- The Third Transmembrane Domain of EscR Is Critical for Function of the EnteropathogenicmSphere · 2018Article
- Interactions of the EphA2 Kinase Domain with PIPs in Membranes: Implications for Receptor Function.Structure (London, England : 1993) · 2018Article
- Fast Calculation of Protein-Protein Binding Free Energies Using Umbrella Sampling with a Coarse-Grained Model.Journal of chemical theory and computation · 2018Article
- Death Receptor 5 Activation Is Energetically Coupled to Opening of the Transmembrane Domain Dimer.Biophysical journal · 2017Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
EphA1 is a receptor tyrosine kinase (RTK) that plays a key role in developmental processes, including guidance of the migration of axons and cells in the nervous system. EphA1, in common with other RTKs, contains an N-terminal extracellular domain, a single transmembrane (TM) α-helix, and a C-terminal intracellular kinase domain. The TM helix forms a dimer, as seen in recent NMR studies. We have modeled the EphA1 TM dimer using a multiscale approach combining coarse-grain (CG) and atomistic molecular dynamics (MD) simulations. The one-dimensional potential of mean force (PMF) for this system, based on interhelix separation, has been calculated using CG MD simulations. This provides a view of the free energy landscape for helix-helix interactions of the TM dimer in a lipid bilayer. The resulting PMF profiles suggest two states, consistent with a rotation-coupled activation mechanism. The more stable state corresponds to a right-handed helix dimer interacting via an N-terminal glycine zipper motif, consistent with a recent NMR structure (2K1K). A second metastable state corresponds to a structure in which the glycine zipper motif is not involved. Analysis of unrestrained CG MD simulations based on representative models from the PMF calculations or on the NMR structure reveals possible pathways of interconversion between these two states, involving helix rotations about their long axes. This suggests that the interaction of TM helices in EphA1 dimers may be intrinsically dynamic. This provides a potential mechanism for signaling whereby extracellular events drive a shift in the repopulation of the underlying TM helix dimer energy landscape.
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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.