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PDBsum entry 2k36
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Viral protein
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PDB id
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2k36
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References listed in PDB file
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Key reference
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Title
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Poxvirus k7 protein adopts a bcl-2 fold: biochemical mapping of its interactions with human dead box RNA helicase ddx3.
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Authors
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A.P.Kalverda,
G.S.Thompson,
A.Vogel,
M.Schröder,
A.G.Bowie,
A.R.Khan,
S.W.Homans.
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Ref.
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J Mol Biol, 2009,
385,
843-853.
[DOI no: ]
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PubMed id
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Abstract
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Poxviruses have evolved numerous strategies to evade host innate immunity.
Vaccinia virus K7 is a 149-residue protein with previously unknown structure
that is highly conserved in the orthopoxvirus family. K7 bears sequence and
functional similarities to A52, which interacts with interleukin
receptor-associated kinase 2 and tumor necrosis factor receptor-associated
factor 6 to suppress nuclear factor kappaB activation and to stimulate the
secretion of the anti-inflammatory cytokine interleukin-10. In contrast to A52,
K7 forms a complex with DEAD box RNA helicase DDX3, thereby suppressing
DDX3-mediated ifnb promoter induction. We determined the NMR solution structure
of K7 to provide insight into the structural basis for poxvirus antagonism of
innate immune signaling. The structure reveals an alpha-helical fold belonging
to the Bcl-2 family despite an unrelated primary sequence. NMR chemical-shift
mapping studies have localized the binding surface for DDX3 on a negatively
charged face of K7. Furthermore, thermodynamic studies have mapped the
K7-binding region to a 30-residue N-terminal fragment of DDX3, ahead of the core
RNA helicase domains.
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Figure 3.
Fig. 3. The BH3 groove of K7 is filled with hydrophobic side
chains. The orientation is the same as in Fig. 1. K7 is coloured
green, and N1 is grey. Side chains are represented as stick
models to emphasize BH3 groove closure by Y67, Y68, and F89 in
K7. The N1 surface is relatively open, although Arg58 of α4
resides along one wall of the BH3 groove.
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Figure 9.
Fig. 9. Viral proteins that adopt the Bcl-2 fold. The family
can be subdivided into two structural groups, those that have a
closed BH3 groove (K7, and likely A52, whose structure is
currently unknown) and N1/M11/M11L, which have open grooves.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2009,
385,
843-853)
copyright 2009.
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