{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T17:23:26Z","timestamp":1785173006252,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,23]]},"group-title":"Developmental Biology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM119557"],"award-info":[{"award-number":["R35GM119557"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The\n                  <jats:italic>Drosophila<\/jats:italic>\n                  Estrogen-Related Receptor (dERR) is an orphan nuclear receptor that regulates developmental metabolism, yet the protein cofactors that modulate its activity remain poorly defined. Here, we used the AI-based FlyPredictome platform to identify candidate dERR interaction partners and evaluate their predicted structural interfaces. Among the highest-confidence interactors is the transcription factor Sima, which represents the\n                  <jats:italic>Drosophila<\/jats:italic>\n                  ortholog of HIF1\u03b1 \u2013 an interaction that was reciprocally identified in both dERR and Sima\/HIF1\u03b1 interaction datasets. Structural modeling predicted binding between the dERR ligand-binding domain and a conserved LXXLL motif in Sima\/HIF1\u03b1. Notably, the predicted dERR\u2013 Sima\/HIF1\u03b1 interaction interface includes residues previously shown to be essential for\n                  <jats:italic>in vitro<\/jats:italic>\n                  binding, providing independent structural support for this biologically relevant protein\u2013protein interaction.\n                <\/jats:p>","DOI":"10.64898\/2026.07.22.739904","type":"posted-content","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T13:55:24Z","timestamp":1784814924000},"source":"Crossref","is-referenced-by-count":0,"title":["Structural modeling supports an interaction between the\n                  <i>Drosophila<\/i>\n                  Estrogen-Related Receptor and Sima\/HIF1\u03b1"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8308-3902","authenticated-orcid":false,"given":"Yuan","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Biology, Indiana University, Bloomington, IN 47405, USA"},{"name":"Medical Sciences, Indiana University, Bloomington, IN 47405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-5683","authenticated-orcid":false,"given":"Jason M.","family":"Tennessen","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana University, Bloomington, IN 47405, USA"},{"name":"Member, Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072709551815000_2026.07.22.739904v1.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.53.082901.104018"},{"key":"2026072709551815000_2026.07.22.739904v1.2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.04.013"},{"key":"2026072709551815000_2026.07.22.739904v1.3","doi-asserted-by":"crossref","unstructured":"Doering, K. R. S. , Cheng, X. , Milburn, L. , Ratnappan, R. , Ghazi, A. , Miller, D. L. & Taubert, S. 2022. Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans. Elife, 11.","DOI":"10.7554\/eLife.67911"},{"key":"2026072709551815000_2026.07.22.739904v1.4","doi-asserted-by":"crossref","first-page":"100815","DOI":"10.1016\/j.jlr.2025.100815","article-title":"The Drosophila estrogen-related receptor promotes triglyceride storage within the larval fat body","volume":"66","year":"2025","journal-title":"J Lipid Res"},{"key":"2026072709551815000_2026.07.22.739904v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.01.011"},{"key":"2026072709551815000_2026.07.22.739904v1.6","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0017"},{"key":"2026072709551815000_2026.07.22.739904v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00444-6"},{"key":"2026072709551815000_2026.07.22.739904v1.8","doi-asserted-by":"crossref","first-page":"375","DOI":"10.31557\/APJCP.2023.24.2.375","article-title":"Unfolding of Imminent Bio-Signatures in the Prognosis of Thyroid Cancer; The Emergence of Estrogen Related Receptor Gamma (ERR\u03b3) as a Hurricane","volume":"24","year":"2023","journal-title":"Asian Pac J Cancer Prev"},{"key":"2026072709551815000_2026.07.22.739904v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"2026072709551815000_2026.07.22.739904v1.10","doi-asserted-by":"crossref","first-page":"102106","DOI":"10.1016\/j.molmet.2025.102106","article-title":"Hypoxia-inducible factor 1\u03b1 is required to establish the larval glycolytic program in Drosophila melanogaster","volume":"93","year":"2025","journal-title":"Mol Metab"},{"key":"2026072709551815000_2026.07.22.739904v1.11","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01538"},{"key":"2026072709551815000_2026.07.22.739904v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.06.016"},{"key":"2026072709551815000_2026.07.22.739904v1.13","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41392-025-02270-3","article-title":"Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions","volume":"10","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"2026072709551815000_2026.07.22.739904v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-021-03819-2"},{"key":"2026072709551815000_2026.07.22.739904v1.15","doi-asserted-by":"crossref","unstructured":"Kim, A. 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