Poison of scorpions is a multi-component substance. Researchers are mainly interested in polypeptide toxins, which affect potential-sensitive sodium channels. These channels are proteins, which allow sodium ions to enter a cell, when a potential of a cell membrane changes. Potential-sensitive sodium channels play a very important role in conducting a nervous impulse and excitability of muscle tissue. When normal functioning of these channels is disturbed by scorpion poison, a victim get paralyzed, or even dies.

Russian researchers study scorpion toxins, able to selectively bind with sodium channels. These studies will help acquire new information about how ion channels – toxin targets – work. Scientists have focused their attention on scorpion α-toxins, which are known to slow down inactivation of potential-sensitive sodium channels and to prolong action potential. Researchers know α-toxins, which affect ion channels of mammals, insects, or both. However, no one still knows which differences in toxin structure are responsible for a selective effect on a certain group of animals. Among possible explanations is a structure of a variable part of a toxin – the so-called RC-domain.

Scientists from the Institute of Biological Chemistry developed a computer model for estimating hydrophobic properties of toxins’ surface and their conformational flexibility. The model revealed that toxins, affecting mammals, had notable difference from two other groups of toxins – their RC-domains were more hydrophilic and flexible, than the rest of the protein molecule.

 

 

Many scorpion toxins are now thoroughly studied, says one of the research authors, but no good explanation of where and how do they bind, as well as why they act selectively depending on a channel type. The answer to these questions is expected to be found – first, using already published data on structure and biochemistry of these molecules, and then – starting own research, based upon building and testing mutant analogues of some toxins.

After mathematical modeling being done, researchers believe that they now have a credible hypothesis of toxin selectivity. Scientists have a strong intention to check whether their idea is right. In case the hypothesis really works, science will obtain an instrument for predicting properties of toxins on the basis of their amino acid sequence and spatial structure. Among other useful things this instrument will help build toxins with given properties for possible use in future and new insecticides, which is very important for agriculture.

The majority of existing insecticides, like DDT (dichloro-diphenyl-trichloroethane) or pyrethroids, act through sodium channel. This is the reason why scorpion toxins might be very helpful in fighting unwanted insects at fields – they are sometimes more effective and selective, than chemicals, and insects fail to develop resistance to scorpion toxins, which often happens in case of “traditional” insecticides. There are several ways to deliver scorpion toxin into insects – they can be incorporated into transgenic agricultural plants, or enter an insect inside an insect virus.