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    Structural Basis for Targeting of Human RNA Helicase DDX3 by Poxvirus Protein K7


    Shun-ichiro, Oda and Schroeder, Martina and Khan, Amir R. (2009) Structural Basis for Targeting of Human RNA Helicase DDX3 by Poxvirus Protein K7. Structure, 11 (17). pp. 1528-1537. ISSN 0969-2126

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    Abstract

    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-κB activation. However, unlike A52, K7 also forms a complex with RNA helicase DDX3 and antagonizes interferon-β 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-β 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.

    Item Type: Article
    Keywords: Structural Basis; Targeting; Human RNA Helicase DDX3; Poxvirus Protein K7;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Item ID: 10686
    Identification Number: https://doi.org/10.1016/j.str.2009.09.005
    Depositing User: Martina Schroeder
    Date Deposited: 04 Apr 2019 09:24
    Journal or Publication Title: Structure
    Publisher: Elsevier
    Refereed: Yes
    URI:

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