Structural basis for corepressor assembly by the orphan nuclear receptor TLX
文献类型：期刊论文
| 作者 | Zhi, Xiaoyong3; Zhou, X. Edward3; He, Yuanzheng3; Searose-Xu, Kelvin3; Zhang, Chun-Li4; Tsai, Chih-Cheng1; Melcher, Karsten3; Xu, H. Eric2,3
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| 刊名 | GENES & DEVELOPMENT
 |
| 出版日期 | 2015-02-15 |
| 卷号 | 29期号:4页码:440-450 |
| 关键词 | COUP PNR SHP TLX |
| ISSN号 | 0890-9369 |
| DOI | 10.1101/gad.254904.114 |
| 文献子类 | Article |
| 英文摘要 | The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX-Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression. |
| WOS关键词 | PROLIFERATOR-ACTIVATED RECEPTORS ; SMALL HETERODIMER PARTNER ; HISTONE DEMETHYLASE LSD1 ; STEM-CELL PROLIFERATION ; GENE TAILLESS ; EMBRYONIC TERMINI ; CRYSTALLOGRAPHY ; REPRESSION ; RECRUITS ; REVEALS |
| 资助项目 | Michigan Technology Tri-Corridor[085P1000817] ; Office of Science of the US Department of Energy[00000000] ; Jay and Betty Van Andel Foundation, Ministry of Science and Technology (China)[2012ZX09301001] ; Jay and Betty Van Andel Foundation, Ministry of Science and Technology (China)[2012CB910403] ; Jay and Betty Van Andel Foundation, Ministry of Science and Technology (China)[2013CB910600] ; Jay and Betty Van Andel Foundation, Ministry of Science and Technology (China)[XDB08020303] ; Jay and Betty Van Andel Foundation, Ministry of Science and Technology (China)[2013ZX09507001] ; National Institute of Health[DK071662] ; National Institute of Health[NS070981] ; National Institute of Health[NS088095] ; National Institute of Health[GM102545] ; National Institute of Health[GM104212] ; Michigan Economic Development Corporation[00000000] |
| WOS研究方向 | Cell Biology ; Developmental Biology ; Genetics & Heredity |
| 语种 | 英语 |
| WOS记录号 | WOS:000349842300009 |
| 出版者 | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276640]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | Xu, H. Eric |
| 作者单位 | 1.Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Andel Res Inst Shanghai Inst Mat Med VARI SIMM, Shanghai 201203, Peoples R China 3.Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA; 4.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 basis for corepressor assembly by the orphan nuclear receptor TLX[J]. GENES & DEVELOPMENT,2015,29(4):440-450. |
| APA | Zhi, Xiaoyong.,Zhou, X. Edward.,He, Yuanzheng.,Searose-Xu, Kelvin.,Zhang, Chun-Li.,...&Xu, H. Eric.(2015).Structural basis for corepressor assembly by the orphan nuclear receptor TLX.GENES & DEVELOPMENT,29(4),440-450. |
| MLA | Zhi, Xiaoyong,et al."Structural basis for corepressor assembly by the orphan nuclear receptor TLX".GENES & DEVELOPMENT 29.4(2015):440-450. |
入库方式： OAI收割
来源：上海药物研究所
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