4MZ7

Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase

4MZ7 の概要

• エントリーDOI: 10.2210/pdb4mz7/pdb
• 分子名称: Deoxynucleoside triphosphate triphosphohydrolase SAMHD1, ZINC ION, 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: hd-domain, hydrolase, dntp binding, phosphorylation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : Q9Y3Z3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 128178.88

構造登録者

Zhu, C.,Gao, W.,Zhao, K.,Qin, X.,Zhang, Y.,Peng, X.,Zhang, L.,Dong, Y.,Zhang, W.,Li, P.,Wei, W.,Gong, Y.,Yu, X.F. (登録日: 2013-09-29, 公開日: 2013-11-20, 最終更新日: 2024-10-30)

主引用文献

Zhu, C.,Gao, W.,Zhao, K.,Qin, X.,Zhang, Y.,Peng, X.,Zhang, L.,Dong, Y.,Zhang, W.,Li, P.,Wei, W.,Gong, Y.,Yu, X.F.
Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase
Nat Commun, 4:2722-2722, 2013

PubMed Abstract: 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-Å 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.

PubMed: 24217394
DOI: 10.1038/ncomms3722

実験手法

X-RAY DIFFRACTION (1.8 Å)