Structural highlights
Function
PG044_VACCW Virulence factor that affects the acute immune response to infection (PubMed:23580427). Bcl-2-like protein which, through its interaction with the DEAD box RNA helicase DDX3X/DDX3, prevents TBK1/IKKepsilon-mediated IRF3 activation. Contributes to virulence by binding to the host TRAF6 and IRAK2 and preventing host NF-kappa-B activation.[1] [2] [3]
Publication Abstract from PubMed
Poxviruses are DNA viruses that express numerous proteins to subvert the host immune response. Vaccinia virus protein K7 adopts a Bcl-2 fold and displays structural and functional similarities to Toll-like receptor antagonist A52. Both proteins interact with IRAK2 and TRAF6 and suppress TLR-dependent NF-kappaB activation. However, unlike A52, K7 also forms a complex with RNA helicase DDX3 and antagonizes interferon-beta promoter induction. We have narrowed the K7 binding site to an N-terminal peptide motif of DDX3 ahead of its core RNA-helicase domains. The crystal structure of full-length K7 in complex with the DDX3 peptide reveals a thumblike projection of tandem phenalyalanine residues of DDX3 into a deep hydrophobic cleft. Mutagenesis of these phenylalanines abolishes the effects of DDX3 on interferon-beta promoter induction. The structure of K7-DDX3 reveals a novel binding mode by a viral Bcl-2 protein that antagonizes a key pathway in innate immunity.
Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7.,Oda S, Schroder M, Khan AR Structure. 2009 Nov 11;17(11):1528-37. PMID:19913487[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schroder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J. 2008 Aug 6;27(15):2147-57. doi: 10.1038/emboj.2008.143. Epub 2008 Jul 17. PMID:18636090 doi:http://dx.doi.org/10.1038/emboj.2008.143
- ↑ Oda S, Schroder M, Khan AR. Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7. Structure. 2009 Nov 11;17(11):1528-37. PMID:19913487 doi:10.1016/j.str.2009.09.005
- ↑ Benfield CTO, Ren H, Lucas SJ, Bahsoun B, Smith GL. Vaccinia virus protein K7 is a virulence factor that alters the acute immune response to infection. J Gen Virol. 2013 Jul;94(Pt 7):1647-1657. PMID:23580427 doi:10.1099/vir.0.052670-0
- ↑ Oda S, Schroder M, Khan AR. Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7. Structure. 2009 Nov 11;17(11):1528-37. PMID:19913487 doi:10.1016/j.str.2009.09.005
