{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:58:52Z","timestamp":1790607532151,"version":"4.1.0"},"reference-count":70,"publisher":"American Chemical Society (ACS)","issue":"18","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["R01EY029169"],"award-info":[{"award-number":["R01EY029169"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["R01AG089561"],"award-info":[{"award-number":["R01AG089561"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["R21AG084065"],"award-info":[{"award-number":["R21AG084065"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ephrin receptors (Ephs) are receptor tyrosine kinases that regulate cellular growth, differentiation, and motility. EphA2, often overexpressed in cancer, is notable for its ligand-independent activation, which drives pro-oncogenic signaling distinct from the canonical, ligand-dependent pathway that restricts cell movement. While ligand binding induces extracellular clustering, kinase activation depends on dimerization within the transmembrane (TM) region. EphA1 and EphA2 differ substantially in their function, likely due to differences in their TM, but more so in their juxtamembrane (JM), and membrane-proximal fibronectin type III (FN1\/FN2) domains. How these latter two regions modulate dimerization has not yet been investigated. To address this, we performed extensive coarse-grained (CG) simulations using Martini3 in an anionic POPC\/PS\/PIP2 model of the plasma membrane. Both receptors formed stable TM dimers, though EphA1 favored a symmetric AXXXGXXXG-centered interface, whereas EphA2 favored an alternate leucine zipper interface. All protein constructs sampled multiple configurations, reflecting substantial intrinsic variability. AlphaFold3 does not yield reliable predictions and cannot account for the effects of the lipid bilayer. In the CG simulations, basic residues in the JM region remained membrane-bound, and the EphA2 FN domain displayed sustained PIP2 interactions, consistent with previous observations. Notably, constructs with the FN2 domain alone (a fragment relevant to Alzheimer's Disease) restricted TM association in both receptors, whereas inclusion of the second FN1 domain restored dimerization but produced receptor-specific extracellular interfaces. These differences arise from distinct FN1-FN2 linker flexibilities, a different level of sequence conservation of EphA1 compared to several other Ephs and FN-domain membrane contacts, which together shape TM geometry and lipid engagement. Our results predict how TM and TM-proximal elements cooperatively tune dimerization in Eph receptors. This work offers a molecular rationale for the divergent activation behaviors of EphA1 and EphA2 and provides testable models relevant to cancer and neurodegeneration biology as well as Eph-driven signaling.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01459","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:18:36Z","timestamp":1788333516000},"page":"12032-12043","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Determinants\nof Receptor-Specific Membrane\nInteractions in EphA1 and EphA2 from Coarse-Grained Simulations"],"prefix":"10.1021","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-9518","authenticated-orcid":true,"given":"Amita Rani","family":"Sahoo","sequence":"first","affiliation":[{"name":"Case Western Reserve University , , 10900 Euclid Avenue , , ,","place":["Cleveland, Ohio, United States, 44106"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"Case Western Reserve University , , 10900 Euclid Avenue , , ,","place":["Cleveland, Ohio, United States, 44106"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Buck","sequence":"additional","affiliation":[{"name":"Case Western Reserve University , , 10900 Euclid Avenue , , ,","place":["Cleveland, Ohio, United States, 44106"]},{"name":"Case Western Reserve University , , 10900 Euclid Avenue , , ,","place":["Cleveland, Ohio, United States, 44106"]},{"name":"Case Western Reserve University , , 10900 Euclid Avenue , , ,","place":["Cleveland, Ohio, United States, 44106"]},{"name":"Case Western Reserve University , , 10900 Euclid Avenue , , ,","place":["Cleveland, Ohio, United States, 44106"]},{"name":"Case Western Reserve University , , 10900 Euclid Avenue , , ,","place":["Cleveland, Ohio, United States, 44106"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"issue":"3\u20134","key":"2026092810073006200_cit1","first-page":"85","article-title":"Global Burden of Cancer","volume":"79","author":"Ma","year":"2006","journal-title":"Yale J. Biol. Med."},{"issue":"10053","key":"2026092810073006200_cit2","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1016\/S0140-6736(16)31012-1","article-title":"Global, Regional, and\nNational Life Expectancy, All-Cause Mortality, and Cause-Specific\nMortality for 249 Causes of Death, 1980\u20132015: A Systematic\nAnalysis for the Global Burden of Disease Study 2015","volume":"388","author":"Wang","year":"2016","journal-title":"Lancet"},{"issue":"5","key":"2026092810073006200_cit3","first-page":"508","article-title":"Cell Cycle Control in Acute Myeloid\nLeukemia","volume":"2","author":"Schnerch","year":"2012","journal-title":"Am. J. Cancer Res."},{"issue":"1","key":"2026092810073006200_cit4","doi-asserted-by":"publisher","DOI":"10.1186\/2049-3002-2-3","article-title":"Hypoxia\nSignaling Pathways in Cancer Metabolism: The\nImportance of Co-Selecting Interconnected Physiological Pathways","volume":"2","author":"Masson","year":"2014","journal-title":"Cancer Metab."},{"key":"2026092810073006200_cit5","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.2147\/DDDT.S89114","article-title":"Receptor Tyrosine\nKinase (c-Kit) Inhibitors: A Potential Therapeutic Target in Cancer\nCells","volume":"10","author":"Babaei","year":"2016","journal-title":"Drug Des., Dev. Ther."},{"issue":"3","key":"2026092810073006200_cit6","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.3390\/cancers7030860","article-title":"Targeting\nRTK Signaling Pathways in Cancer","volume":"7","author":"Regad","year":"2015","journal-title":"Cancers"},{"issue":"6","key":"2026092810073006200_cit7","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1080\/13543784.2020.1762566","article-title":"The Role of Eph\nReceptors in Cancer and How to Target Them: Novel Approaches in Cancer\nTreatment","volume":"29","author":"Buckens","year":"2020","journal-title":"Expert Opin. Invest. Drugs"},{"issue":"3","key":"2026092810073006200_cit8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/nrc2806","article-title":"Eph Receptors\nand Ephrins in Cancer: Bidirectional Signalling and Beyond","volume":"10","author":"Pasquale","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"2026092810073006200_cit9","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1146\/annurev-pharmtox-011112-140226","article-title":"Eph Receptors and\nEphrins: Therapeutic Opportunities","volume":"55","author":"Barquilla","year":"2015","journal-title":"Annu. Rev.\nPharmacol. Toxicol."},{"issue":"10","key":"2026092810073006200_cit10","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1038\/modpathol.3800660","article-title":"Expression Profile\nof Eph Receptors and Ephrin Ligands in Human Skin and Downregulation\nof EphA1 in Nonmelanoma Skin Cancer","volume":"19","author":"Hafner","year":"2006","journal-title":"Mod. Pathol."},{"issue":"7","key":"2026092810073006200_cit11","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1038\/sj.bjc.6604970","article-title":"Epigenetic\nSilencing of EphA1 Expression in Colorectal Cancer Is Correlated with\nPoor Survival","volume":"100","author":"Herath","year":"2009","journal-title":"Br. J. Cancer"},{"issue":"9","key":"2026092810073006200_cit12","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.2174\/156800911798073050","article-title":"EphA2-Dependent\nMolecular Targeting Therapy for Malignant Tumors","volume":"11","author":"Biao-xue","year":"2011","journal-title":"Curr. Cancer Drug Targets"},{"issue":"12","key":"2026092810073006200_cit13","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1158\/1541-7786.MCR-08-0244","article-title":"The EphA2 Receptor\nand EphrinA1 Ligand in Solid Tumors:\nFunction and Therapeutic Targeting","volume":"6","author":"Wykosky","year":"2008","journal-title":"Mol. Cancer\nRes."},{"issue":"1","key":"2026092810073006200_cit14","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00944-9","article-title":"Targeting EphA2 in Cancer","volume":"13","author":"Xiao","year":"2020","journal-title":"J. Hematol. Oncol."},{"issue":"3","key":"2026092810073006200_cit15","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1111\/cas.13942","article-title":"Roles of EphA1\/A2 and\nEphrin-A1 in Cancer","volume":"110","author":"Ieguchi","year":"2019","journal-title":"Cancer Sci."},{"issue":"1","key":"2026092810073006200_cit16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.semcdb.2012.01.001","article-title":"Concepts and Consequences of Eph\nReceptor Clustering","volume":"23","author":"Janes","year":"2012","journal-title":"Semin. Cell Dev. Biol."},{"issue":"1","key":"2026092810073006200_cit17","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cell.2008.03.011","article-title":"Eph-Ephrin\nBidirectional Signaling in Physiology and Disease","volume":"133","author":"Pasquale","year":"2008","journal-title":"Cell"},{"issue":"39","key":"2026092810073006200_cit18","doi-asserted-by":"publisher","first-page":"6567","DOI":"10.1038\/s41388-019-0931-2","article-title":"Eph Receptor\nSignalling: From Catalytic to Non-Catalytic Functions","volume":"38","author":"Liang","year":"2019","journal-title":"Oncogene"},{"issue":"2","key":"2026092810073006200_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.108099","article-title":"Missense Mutations\nof the Ephrin Receptor EPHA1 Associated\nwith Alzheimer\u2019s Disease Disrupt Receptor Signaling Functions","volume":"301","author":"Matsumoto","year":"2025","journal-title":"J. Biol. Chem."},{"key":"2026092810073006200_cit20","doi-asserted-by":"crossref","unstructured":"Kim, Y.; Lasso, G.; Patel, H.; Vardarajan, B.; Santa-Maria, I.; Lefort, R.\n          Alzheimer\u2019s Disease-Associated\nP460L Mutation in Ephrin Receptor Type A1 (EphA1) Leads to Dysregulated\nRho-GTPase Signaling\n          bioRxiv\n          2021\n          10.1101\/2021.06.17.448790.","DOI":"10.1101\/2021.06.17.448790"},{"issue":"3","key":"2026092810073006200_cit21","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1002\/alz.13603","article-title":"Alzheimer\u2019s Disease-Associated P460L Variant of EphA1 Dysregulates\nReceptor Activity and Blood-Brain Barrier Function","volume":"20","author":"Owens","year":"2024","journal-title":"Alzheimer\u2019s Dementia"},{"issue":"20","key":"2026092810073006200_cit22","doi-asserted-by":"publisher","first-page":"2355","DOI":"10.1016\/j.cub.2014.08.028","article-title":"EphA4 Receptor Shedding\nRegulates Spinal Motor Axon Guidance","volume":"24","author":"Gatto","year":"2014","journal-title":"Curr.\nBiol."},{"issue":"1","key":"2026092810073006200_cit23","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2375-1","article-title":"Cross-Talk between the Tissue Factor\/Coagulation\nFactor\nVIIa Complex and the Tyrosine Kinase Receptor EphA2 in Cancer","volume":"16","author":"Eriksson","year":"2016","journal-title":"BMC Cancer"},{"key":"2026092810073006200_cit24","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-1-4939-7595-2_3","article-title":"Identification of Proteolytic Cleavage\nSites of EphA2 by Membrane Type 1 Matrix Metalloproteinase on the\nSurface of Cancer Cells","volume-title":"Proteases and\nCancer","author":"Kikuchi","year":"2018"},{"issue":"47","key":"2026092810073006200_cit25","doi-asserted-by":"publisher","first-page":"32379","DOI":"10.1074\/jbc.M114.599332","article-title":"The Eph Tyrosine\nKinase Receptors\nEphB2 and EphA2 Are Novel Proteolytic Substrates of Tissue Factor\/Coagulation\nFactor VIIa","volume":"289","author":"Eriksson","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2026092810073006200_cit26","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.sbi.2014.10.002","article-title":"Putting\nTogether Structures of Epidermal\nGrowth Factor Receptors","volume":"29","author":"Bessman","year":"2014","journal-title":"Curr. Opin. Struct.\nBiol."},{"issue":"8016","key":"2026092810073006200_cit27","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate Structure Prediction of\nBiomolecular Interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"issue":"6","key":"2026092810073006200_cit28","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.str.2023.03.014","article-title":"Transmembrane\nDimers\nof Type 1 Receptors Sample Alternate Configurations: MD Simulations\nUsing Coarse Grain Martini 3 versus AlphaFold2Multimer","volume":"31","author":"Sahoo","year":"2023","journal-title":"Structure"},{"key":"2026092810073006200_cit29","doi-asserted-by":"crossref","unstructured":"Shrestha, P.; Sahoo, A. R.; Iannucci, M.; Willard, B.; Buck, M.\n          Tyrosine phosphorylation and\nthe inhibitory C-terminal SAM domain regulate the EphA2 intracellular\nfragment in solution: A combined experimental and molecular modeling\nstudy.\n          bioRxiv\n          2025\n          10.1101\/2025.09.29.67 https:\/\/www.biorxiv.org\/content\/10.1101\/2025.09.29.679228v2.","DOI":"10.1101\/2025.09.29.679228"},{"issue":"3","key":"2026092810073006200_cit30","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.cell.2012.12.030","article-title":"Architecture\nand\nMembrane Interactions of the EGF Receptor","volume":"152","author":"Arkhipov","year":"2013","journal-title":"Cell"},{"issue":"2","key":"2026092810073006200_cit31","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.jsb.2009.04.007","article-title":"Ectodomain Orientation, Conformational Plasticity and\nOligomerization of ErbB1 Receptors Investigated by Molecular Dynamics","volume":"167","author":"Ka\u0308stner","year":"2009","journal-title":"J. Struct. Biol."},{"issue":"33","key":"2026092810073006200_cit32","doi-asserted-by":"publisher","first-page":"10611","DOI":"10.1021\/jacs.6b05602","article-title":"Conformational Changes in the Epidermal\nGrowth Factor Receptor: Role of the Transmembrane Domain Investigated\nby Coarse-Grained MetaDynamics Free Energy Calculations","volume":"138","author":"Lelimousin","year":"2016","journal-title":"J. Am. Chem. Soc."},{"issue":"42","key":"2026092810073006200_cit33","doi-asserted-by":"publisher","first-page":"6641","DOI":"10.1021\/bi500800x","article-title":"Dimerization\nof the EphA1 Receptor Tyrosine Kinase Transmembrane Domain: Insights\ninto the Mechanism of Receptor Activation","volume":"53","author":"Chavent","year":"2014","journal-title":"Biochemistry"},{"issue":"18","key":"2026092810073006200_cit100","doi-asserted-by":"publisher","first-page":"167144","DOI":"10.1016\/j.jmb.2021.167144","article-title":"Conformational Clamping\nby a Membrane Ligand Activates the EphA2 Receptor","volume":"433","author":"Westerfield","year":"2021","journal-title":"J Mol Biol."},{"issue":"2","key":"2026092810073006200_cit34","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.str.2015.11.008","article-title":"Structures\nof\nthe EphA2 Receptor at the Membrane: Role of Lipid Interactions","volume":"24","author":"Chavent","year":"2016","journal-title":"Structure"},{"issue":"14","key":"2026092810073006200_cit35","doi-asserted-by":"publisher","first-page":"4334","DOI":"10.1073\/pnas.1503262112","article-title":"N-Glycosylation\nas Determinant of Epidermal Growth Factor Receptor Conformation in\nMembranes","volume":"112","author":"Kaszuba","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"1","key":"2026092810073006200_cit36","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1042\/BST20110632","article-title":"Investigating\nExtracellular in Situ EGFR Structure and Conformational Changes Using\nFRET Microscopy","volume":"40","author":"Roberts","year":"2012","journal-title":"Biochem. Soc. Trans."},{"issue":"11","key":"2026092810073006200_cit37","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1016\/j.cmet.2022.09.023","article-title":"The Role of Lipids\nin Cancer Progression and Metastasis","volume":"34","author":"Martin-Perez","year":"2022","journal-title":"Cell Metab."},{"issue":"2","key":"2026092810073006200_cit38","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s10555-020-09872-z","article-title":"The Role of Lipid Species in Membranes\nand Cancer-Related Changes","volume":"39","author":"Skotland","year":"2020","journal-title":"Cancer Metastasis\nRev."},{"issue":"43","key":"2026092810073006200_cit39","doi-asserted-by":"publisher","first-page":"29385","DOI":"10.1074\/jbc.M803089200","article-title":"Spatial Structure and PH-Dependent\nConformational Diversity of Dimeric Transmembrane Domain of the Receptor\nTyrosine Kinase EphA1","volume":"283","author":"Bocharov","year":"2008","journal-title":"J. Biol. Chem."},{"issue":"5","key":"2026092810073006200_cit40","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/j.bpj.2009.11.008","article-title":"Left-Handed\nDimer of EphA2 Transmembrane Domain: Helix Packing Diversity among\nReceptor Tyrosine Kinases","volume":"98","author":"Bocharov","year":"2010","journal-title":"Biophys. J."},{"issue":"21","key":"2026092810073006200_cit41","doi-asserted-by":"publisher","first-page":"14955","DOI":"10.1074\/jbc.M114.558783","article-title":"Point Mutations in Dimerization Motifs of the Transmembrane\nDomain Stabilize Active or Inactive State of the EphA2 Receptor Tyrosine\nKinase","volume":"289","author":"Sharonov","year":"2014","journal-title":"J. Biol. Chem."},{"issue":"7","key":"2026092810073006200_cit42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107441","article-title":"Transmembrane\nHelix Interactions Regulate Oligomerization of the Receptor Tyrosine\nKinase EphA2","volume":"300","author":"Wirth","year":"2024","journal-title":"J. Biol. Chem."},{"issue":"7","key":"2026092810073006200_cit43","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/embor.2009.91","article-title":"Ligand Recognition\nby A-Class Eph\nReceptors: Crystal Structures of the EphA2 Ligand-Binding Domain and\nthe EphA2\/Ephrin-A1 Complex","volume":"10","author":"Himanen","year":"2009","journal-title":"EMBO Rep."},{"issue":"24","key":"2026092810073006200_cit44","doi-asserted-by":"publisher","first-page":"10860","DOI":"10.1073\/pnas.1004148107","article-title":"Architecture of Eph Receptor Clusters","volume":"107","author":"Himanen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"4","key":"2026092810073006200_cit45","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/nsmb.1782","article-title":"An Extracellular\nSteric Seeding Mechanism for Eph-Ephrin Signaling Platform Assembly","volume":"17","author":"Seiradake","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"issue":"3","key":"2026092810073006200_cit46","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nrm1589","article-title":"Intrinsically Unstructured\nProteins and Their Functions","volume":"6","author":"Dyson","year":"2005","journal-title":"Nat. Rev. Mol.\nCell Biol."},{"issue":"12","key":"2026092810073006200_cit47","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1016\/j.tibs.2024.10.002","article-title":"Eph Receptor\nSignaling Complexes in the Plasma Membrane","volume":"49","author":"Pasquale","year":"2024","journal-title":"Trends Biochem. Sci."},{"issue":"11","key":"2026092810073006200_cit48","doi-asserted-by":"publisher","first-page":"6950","DOI":"10.1074\/jbc.M709202200","article-title":"Spatial Structure\nof the Dimeric\nTransmembrane Domain of the Growth Factor Receptor ErbB2 Presumably\nCorresponding to the Receptor Active State","volume":"283","author":"Bocharov","year":"2008","journal-title":"J. Biol. Chem."},{"issue":"3","key":"2026092810073006200_cit49","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.cell.2012.12.032","article-title":"Conformational Coupling across the\nPlasma Membrane in Activation of the EGF Receptor","volume":"152","author":"Endres","year":"2013","journal-title":"Cell"},{"issue":"16","key":"2026092810073006200_cit50","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168593","article-title":"Structural and Functional Insights\ninto the Transmembrane Domain\nAssociation of Eph Receptors","volume":"22","author":"Sahoo","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"7","key":"2026092810073006200_cit51","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1016\/j.str.2025.03.014","article-title":"Cholesterol-Dependent Dimerization\nand Conformational Dynamics of EphA2 Receptors from Coarse-Grained\nand All-Atom Simulations","volume":"33","author":"Sahoo","year":"2025","journal-title":"Structure"},{"key":"2026092810073006200_cit52","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.00129","article-title":"Structural\nPerspectives on Extracellular\nRecognition and Conformational Changes of Several Type-I Transmembrane\nReceptors","volume":"7","author":"Chataigner","year":"2020","journal-title":"Front. Mol. Biosci."},{"issue":"9 Pt A","key":"2026092810073006200_cit53","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1016\/j.bbamem.2017.01.016","article-title":"Piecing It Together:\nUnraveling the\nElusive Structure-Function Relationship in Single-Pass Membrane Receptors","volume":"1859","author":"Valley","year":"2017","journal-title":"Biochim. Biophys. Acta, Biomembr."},{"issue":"49","key":"2026092810073006200_cit54","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adl0649","article-title":"Phosphatidylinositol\n4,5-Bisphosphate\nDrives the Formation of EGFR and EphA2 Complexes","volume":"10","author":"Singh","year":"2024","journal-title":"Sci. Adv."},{"issue":"1","key":"2026092810073006200_cit55","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-07786-6","article-title":"Cholesterol Inhibits\nAssembly and Oncogenic Activation of the EphA2 Receptor","volume":"8","author":"Schuck","year":"2025","journal-title":"Commun. Biol."},{"issue":"6","key":"2026092810073006200_cit56","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/s41589-020-0529-6","article-title":"Plasma Membranes\nAre Asymmetric in Lipid Unsaturation, Packing and Protein Shape","volume":"16","author":"Lorent","year":"2020","journal-title":"Nat. Chem. Biol."},{"issue":"1","key":"2026092810073006200_cit57","doi-asserted-by":"publisher","DOI":"10.1038\/srep09198","article-title":"The Juxtamembrane\nRegions of Human\nReceptor Tyrosine Kinases Exhibit Conserved Interaction Sites with\nAnionic Lipids","volume":"5","author":"Hedger","year":"2015","journal-title":"Sci. Rep."},{"issue":"5","key":"2026092810073006200_cit58","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1016\/j.bbagen.2014.09.006","article-title":"Interactions\nof the EGFR Juxtamembrane Domain with PIP2-Containing Lipid Bilayers:\nInsights from Multiscale Molecular Dynamics Simulations","volume":"1850","author":"Abd Halim","year":"2015","journal-title":"Biochim. Biophys. Acta, Gen. Subj."},{"key":"2026092810073006200_cit59","unstructured":"Kim, S.; Toth, P.; Wang, W.; Seiradake, E.; Shi, X.; Wang, B.\n          EphA2 and Ephrin-A1 Utilize the Same Interface for\nBoth in Cis and in Trans Interactions That Differentially Regulate\nCell Signaling and Function\n          bioRxiv\n          2025\n          10.1101\/2025.07.31.667925."},{"issue":"10","key":"2026092810073006200_cit60","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1016\/j.bbapap.2013.04.020","article-title":"Eph\/Ephrin Recognition\nand the Role of Eph\/Ephrin Clusters\nin Signaling Initiation","volume":"1834","author":"Nikolov","year":"2013","journal-title":"Biochim. Biophys. Acta,\nProteins Proteomics"},{"issue":"6674","key":"2026092810073006200_cit61","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1126\/science.adg5314","article-title":"Time-Resolved\nLive-Cell\nSpectroscopy Reveals EphA2Multimeric Assembly","volume":"382","author":"Shi","year":"2023","journal-title":"Science"},{"issue":"36","key":"2026092810073006200_cit62","doi-asserted-by":"publisher","first-page":"14634","DOI":"10.1073\/pnas.1311000110","article-title":"Insights into Eph Receptor Tyrosine\nKinase Activation from Crystal Structures of the EphA4 Ectodomain\nand Its Complex with Ephrin-A5","volume":"110","author":"Xu","year":"2013","journal-title":"Proc. Natl.\nAcad. Sci. U.S.A."},{"issue":"5","key":"2026092810073006200_cit63","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1021\/acs.accounts.0c00813","article-title":"Fuzziness and Frustration in the Energy Landscape of\nProtein Folding, Function, and Assembly","volume":"54","author":"Gianni","year":"2021","journal-title":"Acc.\nChem. Res."},{"issue":"18","key":"2026092810073006200_cit64","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.1093\/bioinformatics\/btg362","article-title":"ModLoop: Automated Modeling of Loops\nin Protein Structures","volume":"19","author":"Fiser","year":"2003","journal-title":"Bioinformatics"},{"issue":"W1","key":"2026092810073006200_cit65","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology\nModelling of Protein Structures and Complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"issue":"4","key":"2026092810073006200_cit66","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/s41592-021-01098-3","article-title":"Martini 3: A General Purpose Force\nField for Coarse-Grained\nMolecular Dynamics","volume":"18","author":"Souza","year":"2021","journal-title":"Nat. Methods"},{"key":"2026092810073006200_cit67","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High\nPerformance\nMolecular Simulations through Multi-Level Parallelism from Laptops\nto Supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"issue":"5","key":"2026092810073006200_cit68","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1021\/acs.jctc.5b00209","article-title":"Computational\nLipidomics with Insane: A Versatile Tool for Generating Custom Membranes\nfor Molecular Simulations","volume":"11","author":"Wassenaar","year":"2015","journal-title":"J. Chem. Theory Comput."},{"issue":"6","key":"2026092810073006200_cit69","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1101\/gr.849004","article-title":"WebLogo: A Sequence Logo Generator","volume":"14","author":"Crooks","year":"2004","journal-title":"Genome Res."}],"container-title":["Journal of Chemical Information\nand Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.6c01459","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/18\/12032\/67648345\/acs.jcim.6c01459.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/18\/12032\/67648345\/acs.jcim.6c01459.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:30:01Z","timestamp":1790605801000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article\/66\/18\/12032\/5353677\/Molecular-Determinants-of-Receptor-Specific"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":70,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,8,28]]},"published-print":{"date-parts":[[2026,9,28]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jcim.6c01459","relation":{},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}