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PDBsum entry 3u1n
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References listed in PDB file
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Key reference
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Title
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Hiv-1 restriction factor samhd1 is a deoxynucleoside triphosphate triphosphohydrolase.
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Authors
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D.C.Goldstone,
V.Ennis-Adeniran,
J.J.Hedden,
H.C.Groom,
G.I.Rice,
E.Christodoulou,
P.A.Walker,
G.Kelly,
L.F.Haire,
M.W.Yap,
L.P.De carvalho,
J.P.Stoye,
Y.J.Crow,
I.A.Taylor,
M.Webb.
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Ref.
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Nature, 2011,
480,
379-382.
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PubMed id
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Abstract
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SAMHD1, an analogue of the murine interferon (IFN)-γ-induced gene Mg11 (ref.
1), has recently been identified as a human immunodeficiency virus-1 (HIV-1)
restriction factor that blocks early-stage virus replication in dendritic and
other myeloid cells and is the target of the lentiviral protein Vpx, which can
relieve HIV-1 restriction. SAMHD1 is also associated with Aicardi-Goutières
syndrome (AGS), an inflammatory encephalopathy characterized by chronic
cerebrospinal fluid lymphocytosis and elevated levels of the antiviral cytokine
IFN-α. The pathology associated with AGS resembles congenital viral infection,
such as transplacentally acquired HIV. Here we show that human SAMHD1 is a
potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside
triphosphates to the constituent deoxynucleoside and inorganic triphosphate. The
crystal structure of the catalytic core of SAMHD1 reveals that the protein is
dimeric and indicates a molecular basis for dGTP stimulation of catalytic
activity against dNTPs. We propose that SAMHD1, which is highly expressed in
dendritic cells, restricts HIV-1 replication by hydrolysing the majority of
cellular dNTPs, thus inhibiting reverse transcription and viral complementary
DNA (cDNA) synthesis.
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