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PDBsum entry 2vvy
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Viral protein
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PDB id
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2vvy
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References listed in PDB file
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Key reference
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Title
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Vaccinia virus proteins a52 and b14 share a bcl-2-Like fold but have evolved to inhibit nf-Kappab rather than apoptosis.
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Authors
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S.C.Graham,
M.W.Bahar,
S.Cooray,
R.A.Chen,
D.M.Whalen,
N.G.Abrescia,
D.Alderton,
R.J.Owens,
D.I.Stuart,
G.L.Smith,
J.M.Grimes.
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Ref.
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Plos Pathog, 2008,
4,
e1000128.
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PubMed id
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Abstract
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Vaccinia virus (VACV), the prototype poxvirus, encodes numerous proteins that
modulate the host response to infection. Two such proteins, B14 and A52, act
inside infected cells to inhibit activation of NF-kappaB, thereby blocking the
production of pro-inflammatory cytokines. We have solved the crystal structures
of A52 and B14 at 1.9 A and 2.7 A resolution, respectively. Strikingly, both
these proteins adopt a Bcl-2-like fold despite sharing no significant sequence
similarity with other viral or cellular Bcl-2-like proteins. Unlike cellular and
viral Bcl-2-like proteins described previously, A52 and B14 lack a surface
groove for binding BH3 peptides from pro-apoptotic Bcl-2-like proteins and they
do not modulate apoptosis. Structure-based phylogenetic analysis of 32 cellular
and viral Bcl-2-like protein structures reveals that A52 and B14 are more
closely related to each other and to VACV N1 and myxoma virus M11 than they are
to other viral or cellular Bcl-2-like proteins. This suggests that a progenitor
poxvirus acquired a gene encoding a Bcl-2-like protein and, over the course of
evolution, gene duplication events have allowed the virus to exploit this Bcl-2
scaffold for interfering with distinct host signalling pathways.
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