THE ORIGIN OF THE DIVERSITY OF CROTOXIN ISOFORMS IN THE VENOM OF CROTALUS-DURISSUS-TERRIFICUS

Crotoxin, the main toxin from the venom of the South American rattlesn ake Crotalus durissus terrificus, is a beta-neurotoxin which consists of the non-covalent association of two subunits: a phospholipase A(2) subunit B (CB), and a non-enzymic subunit A (CA). We have previously p urified and characterized several isoforms of each subunit of crotoxin in the venom collected from numerous snakes. Furthermore, three cDNAs encoding two CB isoforms and the precursor, pro-CA, of subunit A have been isolated from a cDNA library prepared from a single venom gland of Crotalus durissus terrificus. The aim of this study is to analyse a n individual snake venom from an animal that has been used to construc t a cDNA library. Several isoforms of subunit A and two isoforms of su bunit B were isolated and compared to purified and characterized subun it isoforms from pooled venom. The result of this study showed that th e multiplicity and the diversity of crotoxin isoforms result from post -translational modifications occurring on a precursor and from the exp ression of different messenger RNAs present in an individual snake. It allowed for the identification of the two CB isoforms encoding cDNAs expressed in the individual venom with two isoforms from pooled venom, CBc and probably CBa2, that belong to two classes of crotoxin complex es which can be distinguished biochemically and pharmacologically.