title: Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains.
abstract: 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.
authors.affiliation: 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.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Egloff
authors.forename: Hélène
authors.initials: H
authors.lastname: Malet
authors.forename: Akos
authors.initials: A
authors.lastname: Putics
authors.forename: Maarit
authors.initials: M
authors.lastname: Heinonen
authors.forename: Hélène
authors.initials: H
authors.lastname: Dutartre
authors.forename: Antoine
authors.initials: A
authors.lastname: Frangeul
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gruez
authors.forename: Valérie
authors.initials: V
authors.lastname: Campanacci
authors.forename: Christian
authors.initials: C
authors.lastname: Cambillau
authors.forename: John
authors.initials: J
authors.lastname: Ziebuhr
authors.forename: Tero
authors.initials: T
authors.lastname: Ahola
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
mesh_terms: 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
chemical_list: C496852:ADP-ribose 1''-phosphate; D006657:Histones; C120756:macroH2A histone; D000246:Adenosine Diphosphate Ribose; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases