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PDBsum entry 3q7c
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References listed in PDB file
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Key reference
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Title
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Structure of the lassa virus nucleoprotein reveals a dsrna-Specific 3' To 5' Exonuclease activity essential for immune suppression.
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Authors
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K.M.Hastie,
C.R.Kimberlin,
M.A.Zandonatti,
I.J.Macrae,
E.O.Saphire.
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Ref.
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Proc Natl Acad Sci U S A, 2011,
108,
2396-2401.
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PubMed id
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Abstract
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Lassa fever virus, a member of the family Arenaviridae, is a highly endemic
category A pathogen that causes 300,000-500,000 infections per year in Western
Africa. The arenaviral nucleoprotein NP has been implicated in suppression of
the host innate immune system, but the mechanism by which this occurs has
remained elusive. Here we present the crystal structure at 1.5 Å of the
immunosuppressive C-terminal portion of Lassa virus NP and illustrate that,
unexpectedly, its 3D fold closely mimics that of the DEDDh family of
exonucleases. Accompanying biochemical experiments illustrate that NP indeed has
a previously unknown, bona fide exonuclease activity, with strict specificity
for double-stranded RNA substrates. We further demonstrate that this exonuclease
activity is essential for the ability of NP to suppress translocation of IFN
regulatory factor 3 and block activation of the innate immune system. Thus, the
nucleoprotein is a viral exonuclease with anti-immune activity, and this work
provides a unique opportunity to combat arenaviral infections.
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