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    Poxvirus K7 Protein Adopts a Bcl-2 Fold: Biochemical Mapping of Its Interactions with Human DEAD Box RNA Helicase DDX3


    Kalverda, Arnout P. and Thompson, Gary S. and Vogel, Andre and Schroeder, Martina and Bowie, Andrew G. and Khan, Amir R. and Homans, Steve W. (2009) Poxvirus K7 Protein Adopts a Bcl-2 Fold: Biochemical Mapping of Its Interactions with Human DEAD Box RNA Helicase DDX3. Journal of Molecular Biology, 385 (3). pp. 843-853. ISSN 0022-2836

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    Abstract

    Poxviruses have evolved numerous strategies to evade host innate immunity. Vaccinia virus K7 is a 149-residue protein with previously unknown structure that is highly conserved in the orthopoxvirus family. K7 bears sequence and functional similarities to A52, which interacts with interleukin receptor-associated kinase 2 and tumor necrosis factor receptor-associated factor 6 to suppress nuclear factor κB activation and to stimulate the secretion of the anti-inflammatory cytokine interleukin-10. In contrast to A52, K7 forms a complex with DEAD box RNA helicase DDX3, thereby suppressing DDX3-mediated ifnb promoter induction. We determined the NMR solution structure of K7 to provide insight into the structural basis for poxvirus antagonism of innate immune signaling. The structure reveals an α-helical fold belonging to the Bcl-2 family despite an unrelated primary sequence. NMR chemical-shift mapping studies have localized the binding surface for DDX3 on a negatively charged face of K7. Furthermore, thermodynamic studies have mapped the K7-binding region to a 30-residue N-terminal fragment of DDX3, ahead of the core RNA helicase domains.

    Item Type: Article
    Additional Information: Cite as: Arnout P. Kalverda, Gary S. Thompson, Andre Vogel, Martina Schröder, Andrew G. Bowie, Amir R. Khan, Steve W. Homans, Poxvirus K7 Protein Adopts a Bcl-2 Fold: Biochemical Mapping of Its Interactions with Human DEAD Box RNA Helicase DDX3, Journal of Molecular Biology, Volume 385, Issue 3, 2009, Pages 843-853, ISSN 0022-2836, https://doi.org/10.1016/j.jmb.2008.09.048. Funding: This work was supported by Science Foundation Ireland (grant 05/RFP/BIC0004 to ARK), and by The University of Leeds.
    Keywords: K7 protein; DDX3 helicase; Bcl-2; nuclear magnetic resonance (NMR) spectroscopy; innate immunity;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 13682
    Identification Number: https://doi.org/10.1016/j.jmb.2008.09.048
    Depositing User: Martina Schroeder
    Date Deposited: 27 Nov 2020 16:46
    Journal or Publication Title: Journal of Molecular Biology
    Publisher: Elsevier
    Refereed: Yes
    Funders: Science Foundation Ireland (SFI)
    URI:

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