Deletions at the C-terminus of interferon gamma reduce RNA binding and activation of double-stranded-RNA cleavage by bovine seminal ribonuclease.
Recombinant interferon gamma (IFN-gamma) from three species activates the cleavage of double stranded (ds-) RNA by the dimeric RNAase isolated from bovine semen (BS-RNAase). Human and bovine IFN-gamma bind RNA tightly enough to inhibit cleavage by RNAase A [Schein, Haugg and Benner (1990) FEBS Lett. 270, 229-232]. Murine IFN-gamma and a proteolytic fragment of human IFN-gamma, both of which lack part of the positively charged C-terminus, bind RNA weakly and do not inhibit RNAase A. Their ability to activate BS-RNAase is proportional to their activity in the anti-viral assay. Two monoclonal antibodies that neutralize the anti-viral activity of human IFN-gamma inhibit the activation of BS-RNAase by both full-length and proteolysed human IFN-gamma. Our results demonstrate that the C-terminus of IFN-gamma contributes to RNA binding and activation of BS-RNAase, as well as to anti-viral activity.
Schein
C H
CH
Swiss Institute for Alternatives to Animal Testing (SIAT), Zürich.
Haugg
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D011994:Recombinant Proteins; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011994:Recombinant Proteins; D007371:Interferon-gamma; D004722:Endoribonucleases; C032523:ribonuclease SPL