Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase
文献类型：期刊论文
| 作者 | Zhu, CF; Gao, WY; Zhao, K; Qin, XH; Zhang, YJ; Peng, X; Zhang, L; Dong, YH; Zhang, WY; Li, P |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2013 |
| 卷号 | 4页码:2722 |
| 英文摘要 | SAMHD1 is a dGTP-activated deoxynucleoside triphosphate triphosphohydrolase (dNTPase) whose dNTPase activity has been linked to HIV/SIV restriction. The mechanism of its dGTP-activated dNTPase function remains unclear. Recent data also indicate that SAMHD1 regulates retrotransposition of LINE-1 elements. Here we report the 1.8-angstrom crystal structure of homotetrameric SAMHD1 in complex with the allosteric activator and substrate dGTP/dATP. The structure indicates the mechanism of dGTP-dependent tetramer formation, which requires the cooperation of three subunits and two dGTP/dATP molecules at each allosteric site. Allosteric dGTP binding induces conformational changes at the active site, allowing a more stable interaction with the substrate and explaining the dGTP-induced SAMHD1 dNTPase activity. Mutations of dGTP binding residues in the allosteric site affect tetramer formation, dNTPase activity and HIV-1 restriction. dGTP-triggered tetramer formation is also important for SAMHD1-mediated LINE-1 regulation. The structural and functional information provided here should facilitate future investigation of SAMHD1 function, including dNTPase activity, LINE-1 modulation and HIV-1 restriction. |
| 学科主题 | Science & Technology - Other Topics |
| 收录类别 | SCI |
| WOS记录号 | WOS:000328021600003 |
| 公开日期 | 2016-05-03 |
| 源URL | [http://ir.ihep.ac.cn/handle/311005/224467]  |
| 专题 | 高能物理研究所_多学科研究中心 |
| 推荐引用方式 GB/T 7714 | Zhu, CF,Gao, WY,Zhao, K,et al. Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase[J]. NATURE COMMUNICATIONS,2013,4:2722. |
| APA | Zhu, CF.,Gao, WY.,Zhao, K.,Qin, XH.,Zhang, YJ.,...&Yu, XF；董宇辉.(2013).Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase.NATURE COMMUNICATIONS,4,2722. |
| MLA | Zhu, CF,et al."Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase".NATURE COMMUNICATIONS 4(2013):2722. |
入库方式： OAI收割
来源：高能物理研究所
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