Taipoxin, an Extremely Potent Presynaptic Neurotoxin from the Venom of the Australian Snake Taipan (Oxyuranus s. scutellatus)

Abstract

Taipoxin (taipan toxin), purified from the venom of the Australian taipan (Oxyuranus s. scutellatus) by gel filtration on Sephadex G-75 followed by column zone electrophoresis, is the most lethal neurotoxin yet isolated from any snake venom. The LD₅₀ is 2 μg/kg in the mouse. The main physiological effect is a gradual reduction to complete stop of evoked and spontaneous release of acetylcholine from motor nerve terminals. Intoxicated animals die of asphyxia caused by neuromuscular blockage of the respiratory muscles. Taipoxin is a moderately acidic sialo-glycoprotein (pI 5) with a molecular weight of 45600 as calculated from composition data or 46800 as determined by meniscus depletion sedimentation equilibrium. Taipoxin is a 1:1:1 ternary complex of subunits designated α, β and γ which dissociate completely at low pH and high ionic strength or in 6 M guanidine hydrochloride. The dissociation by guanidine at neutral pH is reversible, while the acid-induced dissociation is not. The α and β components consist of 120 amino acid residues cross-linked by seven disulfide bridges, whereas the component has 135 residues and eight disulfides. The very basic (pI < 10) a component contains 13 residues of arginine and is the only subunit displaying lethal neurotoxicity (mouse LD₅₀∼ 300 μg/kg): The neutral β fraction was separated by ion-exchange chromatography into two iso-component, β₁ and β₂, which differ slightly in amino acid composition. The very acidic γ component contains all of the carbohydrate, which includes 4-5 residues of sialic aid. The three subunits are homologous in sequence although the γ component is eight residues longer on the N-terminus and must also contain extra amino acids elsewhere