Modes of action of crotoxin and of its binding protein crocalbin
Date Issued
2008
Date
2008
Author(s)
Lee, I-Liang
Abstract
Crotoxin from the South American rattlesnake Crotalus durissus terrificus is a potent presynaptic toxin composed of two subunits: component A and component B. Component B exhibits phospholipase A2 activity and is weakly toxic by itself, whereas no activity has been found to be associated with component A alone. In the present study, we found that component A modulates the neurotoxic effect of component B with a biphasic dose-response curve. In contrast, the phospholipase A2 activity of component B is inhibited monotonically by increasing doses of component A (IC50 ~ 115 pM). In order to resolve the seemingly contradictory observations, we propose a protective semi-receptor model, in which component A acts as a soluble, protective semi-receptor to illuminate the modulatory effect of component A on the interactions of component B with bio-membranes. This model can also account for some other data in the literature. We have also determined the equilibrium dissociation constant Kd for crotoxin subunits to be ~130 pM. Using this value and the semi-receptor model, we unambiguously measured the Kd for the binding of component B to its high-affinity receptor in the neuronal membrane to be ~1.8 nM. The present system represents the first with such a mode of action to be mathematic examination in detail. This model may have important implications in more physiological systems and may also promote to design of agents to reduce the side effects of certain pharmaceuticals.
Subjects
Crotoxin
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