The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket.

Malet, Helene; Coutard, Bruno; Jamal, Said; Dutartre, Helene; Papageorgiou, Nicolas; Neuvonen, Maarit; Ahola, Tero; Forrester, Naomi; Gould, Ernest A.; Lafitte, Daniel; Ferron, Francis; Lescar, Julien; Gorbalenya, Alexander E.; de Lamballerie, Xavier; Canard, Bruno. 2009 The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket. Journal of Virology, 83. 6534-6545. 10.1128/JVI.00189-09

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Abstract/Summary

Macro domains (also called "X domains") constitute a protein module family present in all kingdoms of life, including viruses of the Coronaviridae and Togaviridae families. Crystal structures of the macro domain from the Chikungunya virus (an "Old World" alphavirus) and the Venezuelan equine encephalitis virus (a "New World" alphavirus) were determined at resolutions of 1.65 and 2.30 Å, respectively. These domains are active as adenosine di-phosphoribose 1''-phosphate phosphatases. Both the Chikungunya and the Venezuelan equine encephalitis virus macro domains are ADP-ribose binding modules, as revealed by structural and functional analysis. A single aspartic acid conserved through all macro domains is responsible for the specific binding of the adenine base. Sequence-unspecific binding to long, negatively charged polymers such as poly(ADP-ribose), DNA, and RNA is observed and attributed to positively charged patches outside of the active site pocket, as judged by mutagenesis and binding studies. The crystal structure of the Chikungunya virus macro domain with an RNA trimer shows a binding mode utilizing the same adenine-binding pocket as ADP-ribose, but avoiding the ADP-ribose 1''-phosphate phosphatase active site. This leaves the AMP binding site as the sole common feature in all macro domains.

Item Type:	Publication - Article
Digital Object Identifier (DOI):	10.1128/JVI.00189-09
Programmes:	CEH Topics & Objectives 2009 - 2012 > Biodiversity > BD Topic 2 - Ecological Processes in the Environment
UKCEH and CEH Sections/Science Areas:	Hails
ISSN:	0022-538X
NORA Subject Terms:	Biology and Microbiology
Related URLs:	Publisher
Date made live:	13 Apr 2010 14:50 +0 (UTC)
URI:	https://nora.nerc.ac.uk/id/eprint/9227

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