Download MendeleyStructural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase
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.(2013) Nat Commun 4: 2722-2722
- PubMed: 24217394
- DOI: https://doi.org/10.1038/ncomms3722
- Primary Citation of Related Structures:
4MZ7 - 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.
Organizational Affiliation:
1] School of Life Sciences, Tianjin University, Tianjin 300072, China [2].
