Autor(es): Malet Hélène, Coutard Bruno, Jamal Saïd, Dutartre Hélène, Papageorgiou Nicolas, Neuvonen Maarit, Ahola Tero, Forrester Naomi, Gould Ernest A, Lafitte Daniel, Ferron Francois, Lescar Julien, Gorbalenya Alexander E, de Lamballerie Xavier, Canard Bruno

Resumo: Macro domains (also called X domains") constitute a protein module family present in all kingdoms of life, including viruses of the Coronaviridae - Togaviridae families. Crystal structures of the macro domain from the Chikungunya virus (an "Old World" alphavirus) - the Venezuelan equine encephalitis virus (a "New World" alphavirus) were determined at resolutions of 1.65 - 2.30 A, respectively. These domains are active as adenosine di-phosphoribose 1''-phosphate phosphatases. Both the Chikungunya - the Venezuelan equine encephalitis virus macro domains are ADP-ribose binding modules, as revealed by structural - 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, - RNA is observed - attributed to positively charged patches outside of the active site pocket, as judged by mutagenesis - 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."

Imprenta: Journal of Virology, v. 83, n. 13, p. 6534-6545, 2009

Identificador do objeto digital: 10.1128/JVI.00189-09

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - DNA ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya Virus - Virus

Data de publicação: 2009

INDICADORES

ACESSO