Cobra (Naja Naja Atra) Membrane Toxin Isoforms: Structure and Function

Abstract

Two membrane toxins, termed MT-I and MT-II, were purified to HPLC homogeneity from the venom of Naja naja atra. The NH₂-terminal sequences of the two isoforms were determined. When compared with the known sequences of membrane toxins, we concluded they are CTX-I and CTX-III (from Naja naja atra), respectively. Membrane toxins are basic peptides typified by a chain of 60 amino acids long. Their pi is about 10 and Mr is 6,000-7,000. About half of the amino acids are hydrophobic.

There is lytic synergism between membrane toxins and phospholipase A₂. Membrane toxins, which are different from neurotoxins, are capable of depolarizing muscle cells. The toxins are able to kill cancer cells in vitro. Electrocardiograph of cat to which membrane toxin was applied shows magnificent changes. A positive correlation exists between hydrophobicities and activities of the toxins to inhibit protein kinase C (PKC) activity. All the effects are the result of action of the toxins on cell membranes. In addition, structure-activity relationships are investigated with the available comparative data for membrane toxins centering on LD₅₀, erythrocyte lysis, and muscle cell depolarization.