Ribonucleases with angiogenic and bactericidal activities from the Atlantic salmon.
The importance of fish in vertebrate evolution has been better recognized in recent years after the intense work carried out on fish genomics. The recent discovery that fish genomes comprise homologs of ribonucleases, studied before only in tetrapods, and the isolation of ribonucleases from zebrafish have suggested an experimental model for studying fish and vertebrate evolution. Thus, the cDNAs encoding the RNases from the Atlantic salmon were expressed, and the recombinant RNases (Ss-RNase-1 and Ss-RNase-2) were isolated and characterized as both proteins and for their biological activities. Salmon RNases are less active than RNase A in degrading RNA, but are both sensitive to the action of the human cytosolic RNase inhibitor. The two enzymes possess both angiogenic and bactericidal activities. However, catalytically inactivated Ss-RNases do not exert any angiogenic activity, but preserve their full bactericidal activity, which is surprisingly preserved even when the enzyme proteins are fully denatured. Analyses of the conformational stability of the two RNases has revealed that they are as stable as typical RNases of the superfamily, and Ss-RNase-2, the most active as an enzyme, is also the most resistant to thermal and chemical denaturation. The implications of these findings in terms of the evolution of early RNases, in particular of the physiological significance of the angiogenic and bactericidal activities of fish RNases, are analyzed and discussed.
Pizzo
Elio
E
Department of Structural and Functional Biology, University of Naples Federico II, Via Cintia, Naples, Italy.
Varcamonti
Mario
M
Di Maro
Antimo
A
D Maro
Antimo
A
Zanfardino
Anna
A
Giancola
Concetta
C
D'Alessio
Giuseppe
G
D000595:Amino Acid Sequence; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001681:Biological Assay; D003001:Cloning, Molecular; D004722:Endoribonucleases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004795:Enzyme Stability; D019143:Evolution, Molecular; D029941:Fish Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020317:Salmo salar / Q000235:genetics / Q000502:physiology*
D043925:Angiogenesis Inducing Agents; D000900:Anti-Bacterial Agents; D029941:Fish Proteins; D011994:Recombinant Proteins; D004722:Endoribonucleases; C029494:ribonuclease U; D012259:Ribonuclease, Pancreatic