1NQ7

Characterization of ligands for the orphan nuclear receptor RORbeta

Summary for 1NQ7

• Entry DOI: 10.2210/pdb1nq7/pdb
• Descriptor: NUCLEAR RECEPTOR ROR-BETA, STEROID RECEPTOR COACTIVATOR-1, 7-(3,5-DITERT-BUTYLPHENYL)-3-METHYLOCTA-2,4,6-TRIENOIC ACID, ... (4 entities in total)
• Functional Keywords: ligand-binding domain, retinoids, retinoic acid, synthetic ligand, antagonist, transcription
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Nucleus (Probable): P45446
• Total number of polymer chains: 2
• Total formula weight: 29798.67

Authors

Stehlin-Gaon, C.,Willmann, D.,Sanglier, S.,Van Dorsselaer, A.,Renaud, J.-P.,Moras, D.,Schuele, R. (deposition date: 2003-01-21, release date: 2003-09-23, Last modification date: 2023-08-16)

Primary citation

Stehlin-Gaon, C.,Willmann, D.,Zeyer, D.,Sanglier, S.,Van Dorsselaer, A.,Renaud, J.-P.,Moras, D.,Schuele, R.
All-trans retinoic acid is a ligand for the orphan nuclear receptor RORbeta
Nat.Struct.Biol., 10:820-825, 2003

PubMed Abstract: 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.

PubMed: 12958591
DOI: 10.1038/nsb979

Experimental method

X-RAY DIFFRACTION (1.5 Å)