ArticleProceedings of the National Academy of Sciences of the United States of America2014
The signaling phospholipid PIP3 creates a new interaction surface on the nuclear receptor SF-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 98 citations in OpenAlex.
- Phosphoinositides and inositol phosphates as molecular glues.FEBS letters · 2026Review
- Spatial organization of phosphoinositide signaling.FEBS letters · 2026Review
- Synthesis and characterization of a novel phosphatidylinositol 5-phosphate (PI(5)P) photoaffinity probe.RSC chemical biology · 2026Article
- Structure-guided compound prioritization strategy for virtual screening identifies putative binders for the nuclear receptor LRH-1.bioRxiv : the preprint server for biology · 2026Article
- Lipid transfer proteins and PI4KIIα initiate nuclear p53-phosphoinositide signaling.The Journal of biological chemistry · 2026Article
- Lipidation as a post-translational code for protein liquid-liquid phase separation.Journal of lipid research · 2026Review
- ReducediScience · 2026Article
- Expression and purification of Steroidogenic Factor-1 (NR5A1) nuclear receptor ligand binding domain complexed with the signaling phosphoinositide lipid PI(3,4,5)PMethods in enzymology · 2026Article
- Potential endogenous lipid ligands for the nuclear receptor transcription factor Steroidogenic Factor-1.Advances in biological regulation · 2026Review
- Short-term supplementation of thymol and carvacrol regulates feed intake via the hypothalamic PI3K/AKT/SF-1 pathway and influences intestinal traits in chicks.Frontiers in veterinary science · 2026Article
- Review
- The poly(A) polymerase Star-PAP is regulated by stably associated phosphoinositide messengers.The Journal of biological chemistry · 2025Article
- The oily nucleus- role of phospholipids in genome biology: membrane-directed roles and signaling in the nucleoplasm.Cellular and molecular life sciences : CMLS · 2025Review
- Phosphoinositide signalling in cell motility and adhesion.Nature cell biology · 2025Review
- Plasma membrane and nuclear phosphatidylinositol 4,5-bisphosphate signalling in cancer.Lipids in health and disease · 2025Review
- Phosphoinositide signaling in the nucleus: Impacts on chromatin and transcription regulation.Biology of the cell · 2025Review
- A novel heuristic of rigid docking scores positively correlates with full-length nuclear receptor LRH-1 regulation.Computational and structural biotechnology journal · 2024Article
- Arg1 frommBio · 2024Article
- Hippo and PI5P4K signaling intersect to control the transcriptional activation of YAP.Science signaling · 2024Article
- Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The signaling phosphatidylinositol lipids PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3) bind nuclear receptor 5A family (NR5As), but their regulatory mechanisms remain unknown. Here, the crystal structures of human NR5A1 (steroidogenic factor-1, SF-1) ligand binding domain (LBD) bound to PIP2 and PIP3 show the lipid hydrophobic tails sequestered in the hormone pocket, as predicted. However, unlike classic nuclear receptor hormones, the phosphoinositide head groups are fully solvent-exposed and complete the LBD fold by organizing the receptor architecture at the hormone pocket entrance. The highest affinity phosphoinositide ligand PIP3 stabilizes the coactivator binding groove and increases coactivator peptide recruitment. This receptor-ligand topology defines a previously unidentified regulatory protein-lipid surface on SF-1 with the phosphoinositide head group at its nexus and poised to interact with other proteins. This surface on SF-1 coincides with the predicted binding site of the corepressor DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region on chromosome X), and importantly harbors missense mutations associated with human endocrine disorders. Our data provide the structural basis for this poorly understood cluster of human SF-1 mutations and demonstrates how signaling phosphoinositides function as regulatory ligands for NR5As.
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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.