Structural insights into gene repression by the orphan nuclear receptor SHP
文献类型：期刊论文
| 作者 | Zhi, Xiaoyong5; Zhou, X. Edward5; He, Yuanzheng5; Zechner, Christoph3,4; Suino-Powell, Kelly M.5; Kliewer, Steven A.3,6; Melcher, Karsten5; Mangelsdorf, David J.1,3; Xu, H. Eric2,5
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| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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| 出版日期 | 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. |
| 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 |
| 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研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000329614500063 |
| 出版者 | NATL ACAD SCIENCES |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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