Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains.
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-Angstroms 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.
Egloff
Marie-Pierre
MP
Centre National de la Recherche Scientifique and Universités d'Aix-Marseille I et II, UMR 6098, Architecture et Fonction des Macromolécules Biologiques, Ecole Supérieure d'Ingénieurs de Luminy-Case 925, France.
Malet
Hélène
H
Putics
Akos
A
Heinonen
Maarit
M
Dutartre
Hélène
H
Frangeul
Antoine
A
Gruez
Arnaud
A
Campanacci
Valérie
V
Cambillau
Christian
C
Ziebuhr
John
J
Ahola
Tero
T
Canard
Bruno
B
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D003461:Crystallography; D016752:Hepatitis E virus / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000378:metabolism; D012672:Semliki forest virus / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
C496852:ADP-ribose 1''-phosphate; D006657:Histones; C120756:macroH2A histone; D000246:Adenosine Diphosphate Ribose; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases