3jrv
Structure of poxvirus K7 protein in complex with RNA helicase DDX3
Structural highlights
FunctionPG044_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 PubMedPoxviruses 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 AlsoReferences
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