3KYT

Crystal structure of orphan nuclear receptor RORgamma in complex with natural ligand

3KYT の概要

• エントリーDOI: 10.2210/pdb3kyt/pdb
• 分子名称: Nuclear receptor ROR-gamma, Nuclear receptor coactivator 2, 20-HYDROXYCHOLESTEROL, ... (4 entities in total)
• 機能のキーワード: ror, nuclear receptors, alternative splicing, dna-binding, metal-binding, nucleus, receptor, transcription, transcription regulation, zinc, zinc-finger, acetylation, activator, phosphoprotein, polymorphism, lipid binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus (Probable): P51449; Nucleus: Q15596
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30203.26

構造登録者

Martynowski, D.,Li, Y. (登録日: 2009-12-07, 公開日: 2010-03-16, 最終更新日: 2024-02-21)

主引用文献

Jin, L.,Martynowski, D.,Zheng, S.,Wada, T.,Xie, W.,Li, Y.
Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma.
Mol.Endocrinol., 24:923-929, 2010

PubMed Abstract: The retinoic acid-related orphan receptor gamma (RORgamma) has important roles in development and metabolic homeostasis. Although the biological functions of RORgamma have been studied extensively, no ligands for RORgamma have been identified, and no structure of RORgamma has been reported. In this study, we showed that hydroxycholesterols promote the recruitment of coactivators by RORgamma using biochemical assays. We also report the crystal structures of the RORgamma ligand-binding domain bound with hydroxycholesterols. The structures reveal the binding modes of various hydroxycholesterols in the RORgamma pocket, with the receptors all adopting the canonical active conformation. Mutations that disrupt the binding of hydroxycholesterols abolish the constitutive activity of RORgamma. Our observations suggest an important role for the endogenous hydroxycholesterols in modulating RORgamma-dependent biological processes.

PubMed: 20203100
DOI: 10.1210/me.2009-0507

実験手法

X-RAY DIFFRACTION (2.35 Å)