Structural insights into gene repression by the orphan nuclear receptor SHP

doi:10.1073/pnas.1322827111

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物靶标结构与功能中心

	Structural insights into gene repression by the orphan nuclear receptor SHP
	Zhi, Xiaoyong 5; Zhou, X. Edward 5; He, Yuanzheng 5; Zechner, Christoph 3,4; Suino-Powell, Kelly M.5; Kliewer, Steven A.3,6; Melcher, Karsten 5; Mangelsdorf, David J.1,3; Xu, H. Eric2,5
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2014-01-14
卷号	111 期号:2 页码:839-844
ISSN号	0027-8424
DOI	10.1073/pnas.1322827111
文献子类	Article
英文摘要	Small heterodimer partner (SHP) is an orphan nuclear receptor that functions as a transcriptional repressor to regulate bile acid and cholesterol homeostasis. Although the precise mechanism whereby SHP represses transcription is not known, E1A-like inhibitor of differentiation (EID1) was isolated as a SHP-interacting protein and implicated in SHP repression. Here we present the crystal structure of SHP in complex with EID1, which reveals an unexpected EID1-binding site on SHP. Unlike the classical cofactor-binding site near the C-terminal helix H12, the EID1-binding site is located at the N terminus of the receptor, where EID1 mimics helix H1 of the nuclear receptor ligand-binding domain. The residues composing the SHP-EID1 interface are highly conserved. Their mutation diminishes SHP-EID1 interactions and affects SHP repressor activity. Together, these results provide important structural insights into SHP cofactor recruitment and repressor function and reveal a conserved protein interface that is likely to have broad implications for transcriptional repression by orphan nuclear receptors.
资助项目	Michigan Economic Development Corporation and Michigan Technology[085P1000817] ; Office of Science of the US Department of Energy[00000000] ; Jay and Betty Van Andel Foundation[00000000] ; Ministry of Science and Technology (China)[2012ZX09301001-005] ; Ministry of Science and Technology (China)[2012CB910403] ; Amway (China)[00000000] ; National Institutes of Health[R01 DK071662] ; National Institutes of Health[R01 DK067158] ; National Institutes of Health[T32 DK007307] ; Robert A. Welch Foundation[I-1275] ; Robert A. Welch Foundation[I-1558] ; Howard Hughes Medical Institute[00000000]
WOS关键词	SMALL HETERODIMER PARTNER ; BILE-ACID BIOSYNTHESIS ; NEGATIVE FEEDBACK-REGULATION ; LIGAND-BINDING ; HISTONE DEACETYLASE ; CRYSTAL-STRUCTURE ; MOLECULAR-BASIS ; CELL-CYCLE ; PROTEIN ; LRH-1
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATL ACAD SCIENCES
WOS记录号	WOS:000329614500063
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277229]
专题	药物靶标结构与功能中心
通讯作者	Kliewer, Steven A.
作者单位	1.Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Van Andel Res Inst,Shanghai Inst Mat Med Ctr, Shanghai 201203, Peoples R China 3.Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA; 4.Univ Texas SW Med Ctr Dallas, Div Endocrinol, Dept Internal Med, Dallas, TX 75390 USA; 5.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA; 6.Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA;
推荐引用方式 GB/T 7714	Zhi, Xiaoyong,Zhou, X. Edward,He, Yuanzheng,et al. Structural insights into gene repression by the orphan nuclear receptor SHP[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2014,111(2):839-844.
APA	Zhi, Xiaoyong.,Zhou, X. Edward.,He, Yuanzheng.,Zechner, Christoph.,Suino-Powell, Kelly M..,...&Xu, H. Eric.(2014).Structural insights into gene repression by the orphan nuclear receptor SHP.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,111(2),839-844.
MLA	Zhi, Xiaoyong,et al."Structural insights into gene repression by the orphan nuclear receptor SHP".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111.2(2014):839-844.