title: Asp-ase Activity of the Opossum Granzyme B Supports the Role of Granzyme B as Part of Anti-Viral Immunity Already during Early Mammalian Evolution.
abstract: Granzyme B is one of the key effector molecules in our defense against viruses and intracellular bacteria. This serine protease together with the pore forming protein perforin, induces caspase or Bid-dependent apoptosis in target cells. Here we present the first characterization of a granzyme B homolog, the grathepsodenase, in a non-placental mammal, the American opossum (Monodelphis domestica). The recombinant enzyme was produced in a human cell line and used to study its primary and extended cleavage specificity using a panel of chromogenic substrates and recombinant protein substrates. The opossum granzyme B was found to have a specificity similar to human granzyme B, although slightly less restrictive in its extended specificity. The identification of a granzyme B homolog with asp-ase (cleaving after aspartic acid) specificity in a non-placental mammal provides strong indications that caspase or Bid-dependent apoptosis by a serine protease with a conserved primary specificity has been part of anti-viral immunity since early mammalian evolution. This finding also indicates that an asp-ase together with a chymase were the first two serine protease genes to appear in the mammalian chymase locus.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Thorpe
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Akula
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hellman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D005075:Biological Evolution; D004789:Enzyme Activation; D053804:Granzymes / Q000145:classification / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009893:Opossums; D010802:Phylogeny; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000737:chemistry; D013379:Substrate Specificity; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control*
chemical_list: D011994:Recombinant Proteins; D015843:Serpins; D001224:Aspartic Acid; D053804:Granzymes