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bioRxiv · 10.64898/2026.07.22.739904

Structural modeling supports an interaction between the Drosophila Estrogen-Related Receptor and Sima/HIF-1α

Feng, Y.·Tennessen, J. M.
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Abstract

The Drosophila 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 Drosophila ortholog of HIF1 - an interaction that was reciprocally identified in both dERR and Sima/HIF1 interaction datasets. Structural modeling predicted binding between the dERR ligand-binding domain and a conserved LXXLL motif in Sima/HIF1. Notably, the predicted dERR- Sima/HIF1 interaction interface includes residues previously shown to be essential for in vitro binding, providing independent structural support for this biologically relevant protein-protein interaction.

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Feng, Y., Tennessen, J. M.. 2026-07-23. Structural modeling supports an interaction between the Drosophila Estrogen-Related Receptor and Sima/HIF-1α. https://doi.org/10.64898/2026.07.22.739904

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