1nq7
From Proteopedia
Characterization of ligands for the orphan nuclear receptor RORbeta
Structural highlights
FunctionRORB_RAT Orphan nuclear receptor required for normal postnatal development of rod and cone photoreceptor cells. Regulates transcription of OPN1SW in cone photoreceptor cells by binding the sequence 5'-AGGTCA-3' in the OPN1SW promoter. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRetinoids regulate gene expression through binding to the nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In contrast, no ligands for the retinoic acid receptor-related orphan receptors beta and gamma (ROR beta and gamma) have been identified, yet structural data and structure-function analyses indicate that ROR beta is a ligand-regulated nuclear receptor. Using nondenaturing mass spectrometry and scintillation proximity assays we found that all-trans retinoic acid (ATRA) and several retinoids bind to the ROR beta ligand-binding domain (LBD). The crystal structures of the complex with ATRA and with the synthetic analog ALRT 1550 reveal the binding modes of these ligands. ATRA and related retinoids inhibit ROR beta but not ROR alpha transcriptional activity suggesting that high-affinity, subtype-specific ligands could be designed for the identification of ROR beta target genes. Our results identify ROR beta as a retinoid-regulated nuclear receptor, providing a novel pathway for retinoid action. All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta.,Stehlin-Gaon C, Willmann D, Zeyer D, Sanglier S, Van Dorsselaer A, Renaud JP, Moras D, Schule R Nat Struct Biol. 2003 Oct;10(10):820-5. Epub 2003 Sep 7. PMID:12958591[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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