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

Kalverda, AP, Thompson, GS, Vogel, A, Schröder, M, Bowie, AG, Khan, AR, Homans, SW (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 . pp. 843-853. ISSN 0022-2836. (doi:10.1016/j.jmb.2008.09.048) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1016/j.jmb.2008.09.048

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 kappaB 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 alpha-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
DOI/Identification number: 10.1016/j.jmb.2008.09.048
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: G. Thompson
Date Deposited: 23 Jan 2019 17:54 UTC
Last Modified: 30 May 2019 08:47 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/71814 (The current URI for this page, for reference purposes)
Thompson, GS: https://orcid.org/0000-0001-9399-7636
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