Neurotoxic Proteins in Scorpion Venom

Abstract

Scorpion venoms are complex mixtures of mucous, low molecular weight components (salts and organic compounds) and many basic, neurotoxic proteins (M_R < 8000). These neurotoxins alter the properties of Na channels in excitable cells in three ways. One group of toxins delays inactivation of the Na channel, thereby greatly prolonging the action potential. A second effect, produced by other scorpion toxins, is a transient shift in the voltage dependence of activation, which is demonstrated upon application of a depolarizing pulse. This effect, shown thus far only by toxins from New World species of scorpions, results in an increased tendency of the cell to fire spontaneously and repetitively. The third effect produced by some of the toxins is a reduction of ionic currents (both Na and K currents) with no changes in the kinetics of activation and inactivation. Many observations from pathophysiological studies with scorpion venoms and isolated toxins can be explained on the basis of their effects on Na channels.

The three-dimensional structure of one scorpion toxin (Toxin Var3) is known. Because of homology in the amino acid sequences of many different scorpion toxins, it is believed that the structure proposed for Toxin Var3 from Centruroides sculpturatus (Fig. 2 and 3) is typical of the scorpion toxins in general. Featured in this structure are a dense core of protein secondary structure and a surface hydrophobic patch. Many of the conserved amino acids in the scorpion toxins are associated with this patch thus suggesting that this part of the structure is associated with the biological action of the toxins.