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PDBsum entry 3u1n
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PDB id:
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Hydrolase
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Title:
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Structure of the catalytic core of human samhd1
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Structure:
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Sam domain and hd domain-containing protein 1. Chain: a, b, c, d. Fragment: unp residues 120-626. Synonym: dendritic cell-derived ifng-induced protein, dcip, monocyte protein 5, mop-5. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mop5, samhd1. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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3.10Å
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R-factor:
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0.197
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R-free:
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0.228
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Authors:
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D.C.Goldstone,V.Ennis-Adeniran,P.A.Walker,L.F.Haire,M.Webb,I.A.Taylor
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Key ref:
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D.C.Goldstone
et al.
(2011).
HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.
Nature,
480,
379-382.
PubMed id:
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Date:
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30-Sep-11
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Release date:
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16-Nov-11
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PROCHECK
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Headers
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References
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Q9Y3Z3
(SAMH1_HUMAN) -
Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 from Homo sapiens
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Seq:
Struc:
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626 a.a.
435 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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Nature
480:379-382
(2011)
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PubMed id:
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HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.
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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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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.Ayinde,
N.Casartelli,
and
O.Schwartz
(2012).
Restricting HIV the SAMHD1 way: through nucleotide starvation.
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Nat Rev Microbiol,
10,
675-680.
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G.I.Rice,
P.R.Kasher,
G.M.Forte,
N.M.Mannion,
S.M.Greenwood,
M.Szynkiewicz,
J.E.Dickerson,
S.S.Bhaskar,
M.Zampini,
T.A.Briggs,
E.M.Jenkinson,
C.A.Bacino,
R.Battini,
E.Bertini,
P.A.Brogan,
L.A.Brueton,
M.Carpanelli,
C.De Laet,
P.de Lonlay,
M.Del Toro,
I.Desguerre,
E.Fazzi,
A.Garcia-Cazorla,
A.Heiberg,
M.Kawaguchi,
R.Kumar,
J.P.Lin,
C.M.Lourenco,
A.M.Male,
W.Marques,
C.Mignot,
I.Olivieri,
S.Orcesi,
P.Prabhakar,
M.Rasmussen,
R.A.Robinson,
F.Rozenberg,
J.L.Schmidt,
K.Steindl,
T.Y.Tan,
W.G.van der Merwe,
A.Vanderver,
G.Vassallo,
E.L.Wakeling,
E.Wassmer,
E.Whittaker,
J.H.Livingston,
P.Lebon,
T.Suzuki,
P.J.McLaughlin,
L.P.Keegan,
M.A.O'Connell,
S.C.Lovell,
and
Y.J.Crow
(2012).
Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature.
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Nat Genet,
44,
1243-1248.
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J.D.MacMicking
(2012).
Interferon-inducible effector mechanisms in cell-autonomous immunity.
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Nat Rev Immunol,
12,
367-382.
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J.P.Stoye
(2012).
Studies of endogenous retroviruses reveal a continuing evolutionary saga.
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Nat Rev Microbiol,
10,
395-406.
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T.Hatziioannou,
and
D.T.Evans
(2012).
Animal models for HIV/AIDS research.
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Nat Rev Microbiol,
10,
852-867.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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