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PDBsum entry 2vvy

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protein Protein-protein interface(s) links
Viral protein PDB id
2vvy

 

 

 

 

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Contents
Protein chains
142 a.a. *
* Residue conservation analysis
PDB id:
2vvy
Name: Viral protein
Title: Structure of vaccinia virus protein b14
Structure: Protein b15. Chain: a, b, c, d. Synonym: b14. Engineered: yes
Source: Vaccinia virus. Organism_taxid: 10245. Strain: western reserve. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.69Å     R-factor:   0.224     R-free:   0.244
Authors: S.C.Graham,M.W.Bahar,S.Cooray,R.A.-J.Chen,D.M.Whalen,N.G.A.Abrescia, D.Alderton,R.J.Owens,D.I.Stuart,G.L.Smith,J.M.Grimes
Key ref: S.C.Graham et al. (2008). Vaccinia virus proteins A52 and B14 Share a Bcl-2-like fold but have evolved to inhibit NF-kappaB rather than apoptosis. Plos Pathog, 4, e1000128. PubMed id: 18704168
Date:
12-Jun-08     Release date:   26-Aug-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P24772  (B14_VACCW) -  Protein OPG200 from Vaccinia virus (strain Western Reserve)
Seq:
Struc:
149 a.a.
142 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
Plos Pathog 4:e1000128 (2008)
PubMed id: 18704168  
 
 
Vaccinia virus proteins A52 and B14 Share a Bcl-2-like fold but have evolved to inhibit NF-kappaB rather than apoptosis.
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.
 
  ABSTRACT  
 
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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21153876 D.Coulson, and C.Upton (2011).
Characterization of indels in poxvirus genomes.
  Virus Genes, 42, 171-177.  
21383764 M.M.Rahman, and G.McFadden (2011).
Modulation of NF-κB signalling by microbial pathogens.
  Nat Rev Microbiol, 9, 291-306.  
21334039 S.J.Hansen, J.Rushton, A.Dekonenko, H.S.Chand, G.K.Olson, J.A.Hutt, D.Pickup, C.R.Lyons, and M.F.Lipscomb (2011).
Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection.
  Virology, 412, 411-425.  
20147406 D.G.Diel, G.Delhon, S.Luo, E.F.Flores, and D.L.Rock (2010).
A novel inhibitor of the NF-{kappa}B signaling pathway encoded by the parapoxvirus orf virus.
  J Virol, 84, 3962-3973.  
20195521 G.W.Morgan, M.Hollinshead, B.J.Ferguson, B.J.Murphy, D.C.Carpentier, and G.L.Smith (2010).
Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export.
  PLoS Pathog, 6, e1000785.  
  20230632 J.M.González, and M.Esteban (2010).
A poxvirus Bcl-2-like gene family involved in regulation of host immune response: sequence similarity and evolutionary history.
  Virol J, 7, 59.  
20444990 L.E.McCoy, A.S.Fahy, R.A.Chen, and G.L.Smith (2010).
Mutations in modified virus Ankara protein 183 render it a non-functional counterpart of B14, an inhibitor of nuclear factor kappaB activation.
  J Gen Virol, 91, 2216-2220.  
19708815 B.Perdiguero, and M.Esteban (2009).
The interferon system and vaccinia virus evasion mechanisms.
  J Interferon Cytokine Res, 29, 581-598.  
19369349 C.Myskiw, J.Arsenio, R.van Bruggen, Y.Deschambault, and J.Cao (2009).
Vaccinia virus E3 suppresses expression of diverse cytokines through inhibition of the PKR, NF-kappaB, and IRF3 pathways.
  J Virol, 83, 6757-6768.  
19946139 K.Van Vliet, M.R.Mohamed, L.Zhang, N.Y.Villa, S.J.Werden, J.Liu, and G.McFadden (2009).
Poxvirus proteomics and virus-host protein interactions.
  Microbiol Mol Biol Rev, 73, 730-749.  
19439472 L.Banadyga, K.Veugelers, S.Campbell, and M.Barry (2009).
The fowlpox virus BCL-2 homologue, FPV039, interacts with activated Bax and a discrete subset of BH3-only proteins to inhibit apoptosis.
  J Virol, 83, 7085-7098.  
19851467 M.M.Rahman, M.R.Mohamed, M.Kim, S.Smallwood, and G.McFadden (2009).
Co-regulation of NF-kappaB and inflammasome-mediated inflammatory responses by myxoma virus pyrin domain-containing protein m013.
  PLoS Pathog, 5, e1000635.  
19806153 N.C.Elde, and H.S.Malik (2009).
The evolutionary conundrum of pathogen mimicry.
  Nat Rev Microbiol, 7, 787-797.  
19211746 S.J.Chang, J.C.Hsiao, S.Sonnberg, C.T.Chiang, M.H.Yang, D.L.Tzou, A.A.Mercer, and W.Chang (2009).
Poxvirus host range protein CP77 contains an F-box-like domain that is necessary to suppress NF-kappaB activation by tumor necrosis factor alpha but is independent of its host range function.
  J Virol, 83, 4140-4152.  
19913487 S.Oda, M.Schröder, and A.R.Khan (2009).
Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7.
  Structure, 17, 1528-1537.
PDB code: 3jrv
19836338 T.A.Bowden, A.R.Aricescu, J.E.Nettleship, C.Siebold, N.Rahman-Huq, R.J.Owens, D.I.Stuart, and E.Y.Jones (2009).
Structural plasticity of eph receptor A4 facilitates cross-class ephrin signaling.
  Structure, 17, 1386-1397.
PDB codes: 2wo1 2wo2 2wo3
19366914 T.H.Mogensen (2009).
Pathogen recognition and inflammatory signaling in innate immune defenses.
  Clin Microbiol Rev, 22, 240.  
18830408 A.Mathew, J.O'Bryan, W.Marshall, G.J.Kotwal, M.Terajima, S.Green, A.L.Rothman, and F.A.Ennis (2008).
Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus.
  PLoS ONE, 3, e3323.  
18796705 A.S.Fahy, R.H.Clark, E.F.Glyde, and G.L.Smith (2008).
Vaccinia virus protein C16 acts intracellularly to modulate the host response and promote virulence.
  J Gen Virol, 89, 2377-2387.  
18931086 N.Jacobs, N.W.Bartlett, R.H.Clark, and G.L.Smith (2008).
Vaccinia virus lacking the Bcl-2-like protein N1 induces a stronger natural killer cell response to infection.
  J Gen Virol, 89, 2877-2881.  
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. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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