RGD Reference Report - All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta. - Rat Genome Database
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All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta.

Authors: Stehlin-Gaon, C  Willmann, D  Zeyer, D  Sanglier, S  Van Dorsselaer, A  Renaud, JP  Moras, D  Schule, R 
Citation: Stehlin-Gaon C, etal., Nat Struct Biol. 2003 Oct;10(10):820-5. Epub 2003 Sep 7.
RGD ID: 8553609
Pubmed: (View Article at PubMed) PMID:12958591
DOI: Full-text: DOI:10.1038/nsb979

Retinoids 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.

Annotation

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Rorb  (RAR-related orphan receptor B)


Additional Information