2. Academic Validation
  3. Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1

Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1

  • Cell. 2005 Feb 11;120(3):343-55. doi: 10.1016/j.cell.2005.01.024.
Irina N Krylova 1,  Elena P Sablin,  Jamie Moore,  Robert X Xu,  Gregory M Waitt,  J Andrew MacKay,  Dalia Juzumiene,  Jane M Bynum,  Kevin Madauss,  Valerie Montana,  Lioudmila Lebedeva,  Miyuki Suzawa,  Jon D Williams,  Shawn P Williams,  Rodney K Guy,  Joseph W Thornton,  Robert J Fletterick,  Timothy M Willson,  Holly A Ingraham
Affiliations

Affiliation

  • 1 Department of Physiology, University of California, San Francisco, California 94143, USA.
PMID: 15707893 DOI: 10.1016/j.cell.2005.01.024
Abstract

Vertebrate members of the nuclear receptor NR5A subfamily, which includes steroidogenic factor 1 (SF-1) and liver receptor homolog 1 (LRH-1), regulate crucial aspects of development, endocrine homeostasis, and metabolism. Mouse LRH-1 is believed to be a ligand-independent transcription factor with a large and empty hydrophobic pocket. Here we present structural and biochemical data for three Other NR5A members-mouse and human SF-1 and human LRH-1-which reveal that these receptors bind phosphatidyl inositol second messengers and that ligand binding is required for maximal activity. Evolutionary analysis of structure-function relationships across the SF-1/LRH-1 subfamily indicates that ligand binding is the ancestral state of NR5A receptors and was uniquely diminished or altered in the rodent LRH-1 lineage. We propose that Phospholipids regulate gene expression by directly binding to NR5A nuclear receptors.

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