Peer-Reviewed Journal Details
Mandatory Fields
Oda, S;Schroder, M;Khan, AR
2009
November
Structure
Structural Basis for Targeting of Human RNA Helicase DDX3 by Poxvirus Protein K7
Published
45 ()
Optional Fields
BCL-2 FAMILY VIRUS COMPLEX RECOGNITION ACTIVATION VIRULENCE BINDING KINASE MCL-1
17
1528
1537
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-kappa B 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.
CAMBRIDGE
0969-2126
10.1016/j.str.2009.09.005
Grant Details