A Novel Biological Actions Acquired by Ribonuclease Through Oligomerization

M.      Libonati; G.      Gotte; F.      Vottariello

Abstract

After a short introduction with some examples of cytotoxic ribonucleases, the importance of natural or artificial dimerization (oligomerization) as a way for a ribonuclease to acquire novel functional properties has been pointed out. In particular, the role of the three dimensional domain swapping mechanism in bovine pancreatic ribonuclease A oligomerization, as well as its impact for the acquisition of novel biological functions (among which a remarkable antitumor action) by the enzyme protein in oligomeric form have been discussed. Finally, the structural and functional features that could explain why oligomeric ribonuclease A becomes able to display a cytotoxic activity, and the possible use and limits of the three dimensional domain-swapped oligomers of ribonuclease A as anticancer therapeutic agents have been described and discussed.

Keywords: RNase A, RNase A dimers, RNase A oligomers, Cytotoxicity, RNase cytotoxicity, Cytotoxicity of oligomeric RNase A, Antitumor therapy, 3D domain swapping