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:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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