ArticleThe Journal of biological chemistry2010
Structural characterization of the EphA4-Ephrin-B2 complex reveals new features enabling Eph-ephrin binding promiscuity.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 97 citations in OpenAlex.
- Regulatory role of neuronal guidance proteins in spinal cord injury.Neural regeneration research · 2026Article
- Bispecific Ligand-Based EphB4 CAR-T Cells Generated Using Ephrin-B2 Show Potent Antitumor Activity Against Lung Adenocarcinoma.Cancer science · 2026Article
- Master regulators of neurogenesis: the dynamic roles of Ephrin receptors across diverse cellular niches.Translational psychiatry · 2024Review
- Curcumin Allosterically Inhibits the Dengue NS2B-NS3 Protease by Disrupting Its Active Conformation.ACS omega · 2020Article
- Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome.Nature communications · 2020Article
- EphA4/Tie2 crosstalk regulates leptomeningeal collateral remodeling following ischemic stroke.The Journal of clinical investigation · 2020Article
- The Evolutionary History of Ephs and Ephrins: Toward Multicellular Organisms.Molecular biology and evolution · 2020Article
- Identification of Eph receptor signaling as a regulator of autophagy and a therapeutic target in colorectal carcinoma.Molecular oncology · 2019Article
- The first identification of complete Eph-ephrin signalling in ctenophores and sponges reveals a role for neofunctionalization in the emergence of signalling domains.BMC evolutionary biology · 2019Article
- Neuronal EphA4 Regulates OGD/R-Induced Apoptosis by Promoting Alternative Activation of Microglia.Inflammation · 2019Article
- EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through Local Disruption of Adherens Junctions.iScience · 2019Article
- Hypoxia-induced EPHB2 promotes invasive potential of glioblastoma.International journal of clinical and experimental pathology · 2019Article
- Spatiomechanical Modulation of EphB4-Ephrin-B2 Signaling in Neural Stem Cell Differentiation.Biophysical journal · 2018Article
- Theoretical Model of EphA2-Ephrin A1 Inhibition.Molecules (Basel, Switzerland) · 2018Article
- Identification of new EphA4 inhibitors by virtual screening of FDA-approved drugs.Scientific reports · 2018Article
- Identification and characterization of Nanobodies targeting the EphA4 receptor.The Journal of biological chemistry · 2017Article
- Protein-Protein Interactions in Virus-Host Systems.Frontiers in microbiology · 2017Review
- Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants.PloS one · 2017Article
- Dual microRNA Screens Reveal That the Immune-Responsive miR-181 Promotes Henipavirus Entry and Cell-Cell Fusion.PLoS pathogens · 2016Article
- Tiam-Rac signaling mediates trans-endocytosis of ephrin receptor EphB2 and is important for cell repulsion.The Journal of cell biology · 2016Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
EphA and EphB receptors preferentially bind ephrin-A and ephrin-B ligands, respectively, but EphA4 is exceptional for its ability to bind all ephrins. Here, we report the crystal structure of the EphA4 ligand-binding domain in complex with ephrin-B2, which represents the first structure of an EphA-ephrin-B interclass complex. A loose fit of the ephrin-B2 G-H loop in the EphA4 ligand-binding channel is consistent with a relatively weak binding affinity. Additional surface contacts also exist between EphA4 residues Gln(12) and Glu(14) and ephrin-B2. Mutation of Gln(12) and Glu(14) does not cause significant structural changes in EphA4 or changes in its affinity for ephrin-A ligands. However, the EphA4 mutant has approximately 10-fold reduced affinity for ephrin-B ligands, indicating that the surface contacts are critical for interclass but not intraclass ephrin binding. Thus, EphA4 uses different strategies to bind ephrin-A or ephrin-B ligands and achieve binding promiscuity. NMR characterization also suggests that the contacts of Gln(12) and Glu(14) with ephrin-B2 induce dynamic changes throughout the whole EphA4 ligand-binding domain. Our findings shed light on the distinctive features that enable the remarkable ligand binding promiscuity of EphA4 and suggest that diverse strategies are needed to effectively disrupt different Eph-ephrin complexes.
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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.