| 题名 | Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm |
| 作者 | |
| 通讯作者 | Yan, Nieng; Gong, Xin |
| 发表日期 | 2019-05-24
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| DOI | |
| 发表期刊 | |
| ISSN | 2041-1723
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| 卷号 | 10 |
| 摘要 | The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance and regeneration. Inhibition of Hh receptor Patched (Ptch) by the Hh ligands relieves suppression of signaling cascades. Here, we report the cryo-EM structure of tetrameric Ptch1 in complex with the palmitoylated N-terminal signaling domain of human Sonic hedgehog (ShhN(p)) at a 4:2 stoichiometric ratio. The structure shows that four Ptch1 protomers are organized as a loose dimer of dimers. Each dimer binds to one ShhN(p) through two distinct inhibitory interfaces, one mainly through the N-terminal peptide and the palmitoyl moiety of ShhN(p) and the other through the Ca2+-mediated interface on ShhN(p). Map comparison reveals that the cholesteryl moiety of native ShhN occupies a recently identified extracellular steroid binding pocket in Ptch1. Our structure elucidates the tetrameric assembly of Ptch1 and suggests an asymmetric mode of action of the Hh ligands for inhibiting the potential cholesterol transport activity of Ptch1. |
| 相关链接 | [来源记录] |
| 收录类别 | |
| 语种 | 英语
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| 重要成果 | NI期刊
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| 学校署名 | 通讯
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| WOS研究方向 | Science & Technology - Other Topics
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| WOS类目 | Multidisciplinary Sciences
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| WOS记录号 | WOS:000468857900027
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| 出版者 | |
| 来源库 | Web of Science
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| 引用统计 |
被引频次[WOS]：63
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| 成果类型 | 期刊论文 |
| 条目标识符 | http://sustech.caswiz.com/handle/2SGJ60CL/25866 |
| 专题 | 生命科学学院_生物系 |
| 作者单位 | 1.Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA 2.Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Tsinghua Peking Joint Ctr Life Sci, Sch Life Sci,State Key Lab Membrane Biol, Beijing 100084, Peoples R China 3.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China 4.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Guangdong, Peoples R China |
| 通讯作者单位 | 生物系 |
| 推荐引用方式 GB/T 7714 |
Qian, Hongwu,Cao, Pingping,Hu, Miaohui,et al. Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm[J]. Nature Communications,2019,10.
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| APA |
Qian, Hongwu,Cao, Pingping,Hu, Miaohui,Gao, Shuai,Yan, Nieng,&Gong, Xin.(2019).Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm.Nature Communications,10.
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| MLA |
Qian, Hongwu,et al."Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm".Nature Communications 10(2019).
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| 条目包含的文件 | 条目无相关文件。 | |||||
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