Article

Aicardi-Goutieres Syndrome Gene and HIV-1 Restriction Factor SAMHD1 Is a dGTP-regulated Deoxynucleotide Triphosphohydrolas

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 11/2011; 286(51):43596-600. DOI: 10.1074/jbc.C111.317628
Source: PubMed

ABSTRACT The SAMHD1 protein is an HIV-1 restriction factor that is targeted by the HIV-2 accessory protein Vpx in myeloid lineage cells. Mutations in the SAMHD1 gene cause Aicardi-Goutières syndrome, a genetic disease that mimics congenital viral infection. To determine the physiological function of the SAMHD1 protein, the SAMHD1 gene was cloned, recombinant protein was produced, and the catalytic activity of the purified enzyme was identified. We show that SAMHD1 contains a dGTP-regulated deoxynucleotide triphosphohydrolase. We propose that Vpx targets SAMHD1 for degradation in a viral strategy to control cellular deoxynucleotide levels for efficient replication.

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    • "T . E . White et al . / Virology 460 - 461 ( 2014 ) 34 – 44 38 ( Goldstone et al . , 2011 ; Kim et al . , 2012 ; Lahouassa et al . , 2012 ; Powell et al . , 2011 ; White et al . , 2013a ) . To test whether the different human SAMHD1 proteins are affected on their ability to decrease the cellular levels of dNTPs , we measured the levels of dATP , dTTP and dGTP in U937 cells stably expressing the different human SAMHD1 polymorphisms . As shown in Fig . 8 , all tested human SAMHD1 polymorphisms wer"
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    Virology 07/2014; 460(461):34-44. DOI:10.1016/j.virol.2014.04.023 · 3.35 Impact Factor
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    • "). SAMHD1 is a 626 amino acid protein that consists of an amino-terminal SAM domain, a central HD domain and a C-terminal uncharacterized domain (Li et al., 2000; Liao et al., 2008). SAMHD1 is a deoxynucleoside-triphosphate (dNTP) phosphohydrolase (Goldstone et al., 2011; Powell et al., 2011; Yan et al., 2013), which reduces the pool of dNTPs available for reverse transcription both in myeloid cells (Lahouassa et al., 2012; "
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    Frontiers in Microbiology 04/2014; 5:126. DOI:10.3389/fmicb.2014.00126 · 3.94 Impact Factor
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    • "In contrast, LINE-1 inhibition by SAMHD1 is observed in dividing cells. SAMHD1's dNTPase activity depends on residues H167, H206, D207, and D311 within the HD domain (Aravind and Koonin, 1998; Goldstone et al., 2011; Powell et al., 2011) and is crucial for retroviral inhibition because mutations at H206/D207 compromise both enzymatic activity and antiviral potency (Kim et al., 2012; Laguette et al., 2011; Lahouassa et al., 2012). However, in our study, the D311A mutation, which depletes the hydrolase activity of SAMHD1 (Goldstone et al., 2011), still functions as a LINE-1 inhibitor. "
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