EXTENSIVE MULTIPLICITY OF THE MISCELLANEOUS TYPE OF NEUROTOXINS FROM THE VENOM OF THE COBRA NAJA-NAJA-NAJA AND STRUCTURAL CHARACTERIZATION OF MAJOR COMPONENTS

A multiplicity of miscellaneous type neurotoxins were detected in the venom of the cobra Naja naja naja by use of reverse-phase HPLC and FPLC. The primary structures of major forms were determined, giving 4 novel structures. All four contain 62-65 residues, with 10 half-cystine residues and resemble the miscellaneous type of toxins from other Naja species. Differences within the species are extensive, exchanges occur at 27 positions, giving only 58% residue identity between all forms. However, the differences are largely limited to 3 regions corresponding to structurally important loops where two functional residues participating in receptor binding are exchanged. The four miscellaneous neurotoxins now characterized, together with the minor components of the miscellaneous type, the minimally four neurotoxins reported before, and other related toxins, indicate the existence of an extensive toxin gene multiplicity.