1N4H

Characterization of ligands for the orphan nuclear receptor RORbeta

1N4H の概要

• エントリーDOI: 10.2210/pdb1n4h/pdb
• 関連するPDBエントリー: 1K4W 2lbd
• 分子名称: Nuclear Receptor ROR-beta, Steroid Receptor Coactivator-1, RETINOIC ACID, ... (4 entities in total)
• 機能のキーワード: alpha-helical sandwich, protein-peptide-ligand complex, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Nucleus (Probable): P45446
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31669.80

構造登録者

Stehlin-Gaon, C.,Willmann, D.,Sanglier, S.,Van Dorsselaer, A.,Renaud, J.-P.,Moras, D.,Schuele, R. (登録日: 2002-10-31, 公開日: 2003-09-23, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.1 Å)