Open AccessStructural and Functional Basis for ADP-Ribose and Poly(ADP-Ribose) Binding by Viral Macro Domains
Author(s) -
MariePierre Egloff,
Hélène Malet,
Ákos Putics,
Maarit Hein,
Hélène Dutartre,
Antoine Frangeul,
Arnaud Gruez,
Valérie Campanacci,
Christian Cambillau,
John Ziebuhr,
Tero Ahola,
Bruno Canard
Publication year - 2006
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.00713-06
Subject(s) - biology , viral protein , semliki forest virus , ribose , poly adp ribose polymerase , polymerase , rna , virology , virus , microbiology and biotechnology , biochemistry , dna , gene , enzyme
Macro domains constitute a protein module family found associated with specific histones and proteins involved in chromatin metabolism. In addition, a small number of animal RNA viruses, such as corona- and toroviruses, alphaviruses, and hepatitis E virus, encode macro domains for which, however, structural and functional information is extremely limited. Here, we characterized the macro domains from hepatitis E virus, Semliki Forest virus, and severe acute respiratory syndrome coronavirus (SARS-CoV). The crystal structure of the SARS-CoV macro domain was determined at 1.8-Å resolution in complex with ADP-ribose. Information derived from structural, mutational, and sequence analyses suggests a close phylogenetic and, most probably, functional relationship between viral and cellular macro domain homologs. The data revealed that viral macro domains have relatively poor ADP-ribose 1"-phosphohydrolase activities (which were previously proposed to be their biologically relevant function) but bind efficiently free and poly(ADP-ribose) polymerase 1-bound poly(ADP-ribose) in vitro. Collectively, these results suggest to further evaluate the role of viral macro domains in host response to viral infection.