Interaction between DNA and viscotoxins. Cytotoxic basic polypeptides from Viscum album L.

Cytotoxic viscotoxins I, II, III and IVb protect the native structure of DNA against thermal denaturation. Viscotoxin IVb-DNA complexes, obtained by direct mixing, were studied in detail by the techniques of thermal denaturation of DNA and circular dichroism (CD). The binding of viscotoxin IVb to DNA is principally ionic. This interaction results in DNA segments of different thermal stability, probably due to the cooperativity of the binding process. CD studies disclosed that conformation of DNA remains unaltered upon complexing with viscotoxin IVb. The content of alpha-helical structure, appreciable in free viscotoxin IVb, is reduced only slightly in the complexes with an excess of DNA and drastically at the polypeptide-DNA ratios close to saturation. Stoichiometry at the saturation level has been estimated as approximately one molecule of viscotoxin IVb per ten nucleotide residues. The binding of heat-denatured, noncytotoxic viscotoxin IVb to DNA is random, in contrast to the native polypeptide, although the overall stabilization of DNA-double helix is similar in both cases. The presented studies demonstrated that the cytotoxic viscotoxins bind to DNA and that viscotoxin IVb-DNA interaction has some common features with the interaction of various histones with DNA; however, the relevance of the interaction with DNA to the cytotoxic properties of viscotoxins remains unknown.