title: A non-canonical lon proteinase lacking the ATPase domain employs the ser-Lys catalytic dyad to exercise broad control over the life cycle of a double-stranded RNA virus.
abstract: We have identified a region related to the protease domain of bacterial and organelle ATP-dependent Lon proteases in virus protein 4 (VP4) of infectious bursal disease virus strain P2 (IBDVP2), a two-segmented double-stranded RNA virus. Unlike canonical Lons, IBDVP2 VP4 possesses a proteinase activity though it lacks an ATPase domain. Ser652 and Lys692 of IBDVP2 VP4 are conserved across the Lon/VP4 family and are essential for catalysis. Lys692 has the properties of a general base, increasing the nucleophilicity of Ser652; a similar catalytic dyad may function in the other Lons. VP4 can cleave in trans and is responsible for the interdomain proteolytic autoprocessing of the pVP2- VP4-VP3 polyprotein encoded by RNA segment A. VP2, which is later derived from pVP2, and VP3 are major capsid proteins of birnaviruses. Results of the characterization of a range of the IBDVP2 VP4 mutants in cell cultures implicate VP4 in trans-activation of the synthesis of VP1, putative RNA-dependent RNA polymerase encoded by RNA segment B, and in cleavage rate-dependent control of process(es) crucial for the generation of the infectious virus progeny.
authors.affiliation: Institute of Molecular Biology, Friedrich-Loeffler-Institutes, Federal Research Centre for Virus Disease of Animals, D-174988 Insel Riems, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Birghan
authors.forename: E
authors.initials: E
authors.lastname: Mundt
authors.forename: A E
authors.initials: AE
authors.lastname: Gorbalenya
mesh_terms: D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007243:Infectious bursal disease virus / Q000502:physiology*; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D015534:Trans-Activators; C107669:VP1 protein, infectious bursal disease virus; C082513:VP2 protein, infectious bursal disease virus; D015678:Viral Structural Proteins; D012694:Serine; D000255:Adenosine Triphosphate; D049069:ATP-Dependent Proteases; D012697:Serine Endopeptidases; C404159:virus protein 4, infectious bursal disease virus strain P2; D000251:Adenosine Triphosphatases; D008239:Lysine