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PDBsum entry 4u2x
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Viral protein
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PDB id
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4u2x
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References listed in PDB file
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Key reference
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Title
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Ebola virus vp24 targets a unique nls binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated stat1.
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Authors
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W.Xu,
M.R.Edwards,
D.M.Borek,
A.R.Feagins,
A.Mittal,
J.B.Alinger,
K.N.Berry,
B.Yen,
J.Hamilton,
T.J.Brett,
R.V.Pappu,
D.W.Leung,
C.F.Basler,
G.K.Amarasinghe.
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Ref.
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Cell Host Microbe, 2014,
16,
187-200.
[DOI no: ]
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PubMed id
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Abstract
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During antiviral defense, interferon (IFN) signaling triggers nuclear transport
of tyrosine-phosphorylated STAT1 (PY-STAT1), which occurs via a subset of
karyopherin alpha (KPNA) nuclear transporters. Many viruses, including Ebola
virus, actively antagonize STAT1 signaling to counteract the antiviral effects
of IFN. Ebola virus VP24 protein (eVP24) binds KPNA to inhibit PY-STAT1 nuclear
transport and render cells refractory to IFNs. We describe the structure of
human KPNA5 C terminus in complex with eVP24. In the complex, eVP24 recognizes a
unique nonclassical nuclear localization signal (NLS) binding site on KPNA5 that
is necessary for efficient PY-STAT1 nuclear transport. eVP24 binds KPNA5 with
very high affinity to effectively compete with and inhibit PY-STAT1 nuclear
transport. In contrast, eVP24 binding does not affect the transport of classical
NLS cargo. Thus, eVP24 counters cell-intrinsic innate immunity by selectively
targeting PY-STAT1 nuclear import while leaving the transport of other cargo
that may be required for viral replication unaffected.
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