title: Functional and biochemical characterization of the baculovirus caspase inhibitor MaviP35.
abstract: Many viruses express proteins which prevent the host cell death that their infection would otherwise provoke. Some insect viruses suppress host apoptosis through the expression of caspase inhibitors belonging to the P35 superfamily. Although a number of P35 relatives have been identified, Autographa californica (Ac) P35 and Spodoptera littoralis (Spli) P49 have been the most extensively characterized. AcP35 was found to inhibit caspases via a suicide substrate mechanism: the caspase cleaves AcP35 within its 'reactive site loop' then becomes trapped, irreversibly bound to the cleaved inhibitor. The Maruca vitrata multiple nucleopolyhedrovirus encodes a P35 family member (MaviP35) that exhibits 81% identity to AcP35. We found that this relative shared with AcP35 the ability to inhibit mammalian and insect cell death. Caspase-mediated cleavage within the MaviP35 reactive site loop occurred at a sequence distinct from that in AcP35, and the inhibitory profiles of the two P35 relatives differed. MaviP35 potently inhibited human caspases 2 and 3, DCP-1, DRICE and CED-3 in vitro, but (in contrast to AcP35) only weakly suppressed the proteolytic activity of the initiator human caspases 8, 9 and 10. Although MaviP35 inhibited the AcP35-resistant caspase DRONC in yeast, and was sensitive to cleavage by DRONC in vitro, MaviP35 failed to inhibit the proteolytic activity of bacterially produced DRONC in vitro.
authors.affiliation: Department of Biochemistry, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: I L
authors.initials: IL
authors.lastname: Brand
authors.forename: M M
authors.initials: MM
authors.lastname: Green
authors.forename: S
authors.initials: S
authors.lastname: Civciristov
authors.forename: D
authors.initials: D
authors.lastname: Pantaki-Eimany
authors.forename: C
authors.initials: C
authors.lastname: George
authors.forename: T R
authors.initials: TR
authors.lastname: Gort
authors.forename: N
authors.initials: N
authors.lastname: Huang
authors.forename: R J
authors.initials: RJ
authors.lastname: Clem
authors.forename: C J
authors.initials: CJ
authors.lastname: Hawkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D016367:Baculoviridae / Q000378:metabolism*; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D007915:Lepidoptera / Q000821:virology; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D016415:Sequence Alignment; D018411:Spodoptera / Q000821:virology; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D061945:Caspase Inhibitors; C117171:P49 protein, Spodoptera littoralis nucleopolyhedrovirus; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014764:Viral Proteins; C492234:p35 protein, Baculovirus; D020169:Caspases