Crotoxin complex

THE CROTOXIN COMPLEX, A STRIKING MODEL OF COMPLEMENTARITY BETWEEN TWO SUBUNITS... 

Riibsamen, K., Breithaupt, H. and Habermann, E. (1971) Biochemistry and pharmacology of the crotoxin complex. Naunyn Schmiedebergs Arch. Pharmacol. 270, 274-288. 

Since subunit A did not bind to the membranes in the end of the equilibrium binding assay, obviously the dissociation of the crotoxin complex at some point is an important step in the action of the toxin. Hendon and Tu (28) converted crotoxin complex into a non-dis-sociable conjugate by cross-linking the two subunits with a bifunctional cross-linker, dimethyl suberimidate. This conversion abolished the lethality of crotoxin but did not significantly reduce its PLA2 activity. When we used the non-dissociable crotoxin in binding... 

Crotoxin. Main component of the snake venoms of rattlesnakes (Crotalinae). It is a complex of a basic phospholipase A2 (C. B, Mr 13 500) with an acidic protein (C. A, Mr 10000) which transports the phospholipase to its site of action, the presynaptic membrane of the neuromuscular end-plates. Poisoning leads to local pain and necrosis. Systemic sequelae are tiredness, collapse, and shock through to death. In addition to the neurotoxicity, C. also has hemolytic action. 

The synergistic behavior of crotoxin subunits was further demonstrated by studying the differential stability of crotoxin isoforms differing in their toxicity and their enzymatic activity (Faure et al. 1993). More toxic isoforms are less enzymatically active, block neuromuscular transmission of chick biventer cervicis more efficiently, are more stable and dissociate more slowly than less toxic complexes. Therefore, less toxic crotoxin isoforms, because of their lower stability, are more likely to dissociate en route before reaching their target, CA being no more able to prevent CB non specific binding. 

Faure, G., Harvey, A.L., Thomson, E., Saliou, B., Radvanyi, F. and Bon, C. (1993) Comparison of crotoxin isoforms reveals that stability of the complex plays a major role in its pharmacological action. Eur. J. Biochim. 214, 491-496. 

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