Structural Basis for Hydroxycholesterols as Natural Ligands of Orphan Nuclear Receptor ROR gamma

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	Structural Basis for Hydroxycholesterols as Natural Ligands of Orphan Nuclear Receptor ROR gamma
	Jin, Lihua ; Martynowski, Dariusz ; Zheng, Songyang ; Wada, Taira ; Xie, Wen ; Li, Yong ; Jin LH(金利华) ; Li Y(李勇)
刊名	http://dx.doi.org/10.1210/me.2009-0507
	2010-05
关键词	ALPHA LXR OXYSTEROLS IDENTIFICATION CHOLESTEROL RECRUITMENT METABOLISM ACTIVATION PATHWAY
英文摘要	National Institutes of Health [DK081757]; American Heart Association; Science Planning Program of Fujian Province [2009J1010]; 111 Project [B06016]; The retinoic acid-related orphan receptor gamma (ROR gamma) has important roles in development and metabolic homeostasis. Although the biological functions of ROR gamma have been studied extensively, no ligands for ROR gamma have been identified, and no structure of ROR gamma has been reported. In this study, we showed that hydroxycholesterols promote the recruitment of coactivators by ROR gamma using biochemical assays. We also report the crystal structures of the ROR gamma ligand-binding domain bound with hydroxycholesterols. The structures reveal the binding modes of various hydroxycholesterols in the ROR gamma pocket, with the receptors all adopting the canonical active conformation. Mutations that disrupt the binding of hydroxycholesterols abolish the constitutive activity of ROR gamma. Our observations suggest an important role for the endogenous hydroxycholesterols in modulating ROR gamma 6-dependent biological processes. (Molecular Endocrinology 24: 923-929, 2010)
语种	英语
出版者	MOL ENDOCRINOL
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/90491]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Jin, Lihua,Martynowski, Dariusz,Zheng, Songyang,et al. Structural Basis for Hydroxycholesterols as Natural Ligands of Orphan Nuclear Receptor ROR gamma[J]. http://dx.doi.org/10.1210/me.2009-0507,2010.
APA	Jin, Lihua.,Martynowski, Dariusz.,Zheng, Songyang.,Wada, Taira.,Xie, Wen.,...&李勇.(2010).Structural Basis for Hydroxycholesterols as Natural Ligands of Orphan Nuclear Receptor ROR gamma.http://dx.doi.org/10.1210/me.2009-0507.
MLA	Jin, Lihua,et al."Structural Basis for Hydroxycholesterols as Natural Ligands of Orphan Nuclear Receptor ROR gamma".http://dx.doi.org/10.1210/me.2009-0507 (2010).