Basic homopolyamino acids, histones and protamines are potent antagonists of angiogenin binding to ribonuclease inhibitor

A radio-ribonuclease inhibitor assay based on the interaction of I-125-angi ogenin with ribonuclease inhibitor (RI) was used to detect pancreatic-type ribonucleases and potential modulators of their action. We show that highly basic proteins including the homopolypeptides poly-arginine, poly-lysine a nd poly-ornithine, core histones, spermatid-specific S1 protein and the pro tamines HP3 and Z3 were strong inhibitors of angiogenin binding to RI. A mi nimum size of poly-arginine and poly-lysine was required for efficient inhi bition, The inhibition likely resulted from direct association of the basic proteins with the acidic inhibitor, as RI bound to poly-lysine and protami nes while I-125- angiogenin did not, Antagonists of the angiogenin-R1 inter action are potential regulators of either angiogenin-triggered angiogenesis and/or intracellular RI function, depending on their preferential target. (C) 1999 Federation of European Biochemical Societies.