1N83

Crystal Structure of the complex between the Orphan Nuclear Hormone Receptor ROR(alpha)-LBD and Cholesterol

1N83 の概要

• エントリーDOI: 10.2210/pdb1n83/pdb
• 分子名称: Nuclear receptor ROR-alpha, CHOLESTEROL (3 entities in total)
• 機能のキーワード: three-layered alpha helical sandwich, receptor, transcription regulation, nuclear protein, dna binding, lipid binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P35398
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31900.93

構造登録者

Kallen, J.A.,Schlaeppi, J.M.,Bitsch, F.,Geisse, S.,Geiser, M.,Delhon, I.,Fournier, B. (登録日: 2002-11-19, 公開日: 2002-12-11, 最終更新日: 2024-02-14)

主引用文献

Kallen, J.A.,Schlaeppi, J.M.,Bitsch, F.,Geisse, S.,Geiser, M.,Delhon, I.,Fournier, B.
X-ray Structure of hROR(alpha) LBD at 1.63A: Structural and Functional data that Cholesterol or a Cholesterol derivative is the natural ligand of ROR(alpha)
Structure, 10:1697-1702, 2002

PubMed Abstract: The retinoic acid-related orphan receptor alpha (RORalpha) is an orphan member of the subfamily 1 of nuclear hormone receptors. No X-ray structure of RORalpha has been described so far, and no ligand has been identified. We describe the first crystal structure of the ligand binding domain (LBD) of RORalpha, at 1.63 A resolution. This structure revealed a ligand present in the ligand binding pocket (LBP), which was identified by X-ray crystallography as cholest-5-en-3beta-ol (cholesterol). Moreover, RORalpha transcriptional activity could be modulated by changes in intracellular cholesterol level or mutation of residues involved in cholesterol binding. These findings suggest that RORalpha could play a key role in the regulation of cholesterol homeostasis and thus represents an important drug target in cholesterol-related diseases.

PubMed: 12467577
DOI: 10.1016/S0969-2126(02)00912-7

実験手法

X-RAY DIFFRACTION (1.63 Å)