28th ANNUAL EASTERN FISH HEALTH WORKSHOP April 21-25, 2003 A Novel Effector Molecule Of Catfish NCC Is A Precursor Of The Mammalian Gramzyme Family Kesavannair Praveen, John H Leary III, and Liliana Jaso-Friedmann Department of Medical Microbiology and Parasitology, College of Veterinary Medicine, University of Georgia, Agriculture Drive, Athens, GA 30602 Granzymes are granule associated serine proteases, which are important effector molecules in NK cell and CTL functions. More than 10 different granzymes have been reported from human, mouse and rat. The granzyme family poses a perplexing problem in phylogenetics due to the lack of sequence information from other organisms. We now report the identification of a cDNA that codes for a granzyme homolog from nonspecific cytotoxic cells (NCC) of a teleost. These cells are the evolutionary precursors of NK cells. Catfish granzyme cDNA encoded a protein containing 246 amino acids with ~38-50% similarities to other known granzymes. Comparison of its amino acid sequence with other serine proteases enabled the prediction of substrate specificity, based on the location of highly conserved catalytic triad residues, specificity pocket residues and other motifs common to granzymes. Phylogenetic tree analysis showed clustering of fish granzyme with granzyme K genes. These data suggest that this fish granzyme may be an evolutionary precursor for granzyme K in higher vertebrates. Molecular modeling of the catfish granzyme using known serine protease structures revealed the presence of four highly conserved disulfide linkages. By analogy it is believed that this molecule may play an important role in the effector functions of nonspecific cytotoxic cells of fish. This research was supported by funding from USDA Grant # 98-35205-6701. Return to 28th Annual Eastern Fish Health Workshop Return to Leetown Science Center Home Page