Voltage-gated sodium channels are a major target for toxins and insecticides due to their central role in excitability, but due to the conservation of these channels in Animalia most insecticides do not distinguish between those of insects and mammals, thereby imposing risks to humans and livestock. Evidently, as long as modern agriculture depends heavily on the use of insecticides there is a great need for new substances capable of differentiating between sodium channel subtypes. Such substances exist in venomous animals, but ways for their exploitation have not yet been developed due to problems associated with manufacturing, degradation, and delivery to the target channels. Engineering of plants for expression of anti-insect toxins or use of natural vectors that express toxins near their target site (e.g. baculoviruses) are still problematic and raise public concern. In this problematic reality a rational approach might be to learn from nature how to design highly selective anti-insect compounds preferably in the form of peptidomimetics. This is a complex task that requires the elucidation of the face of interaction between insect-selective toxins and their sodium channel receptor sites. This review delineates current progress in: (i) elucidation of the bioactive surfaces of scorpion β-toxins, especially the excitatory and depressant groups, which show high preference for insects and bind insect sodium channels with high affinity; (ii) studies of the mode of interaction of scorpion β-toxins with receptor site-4 on voltage-gated sodium channels; and (iii) clarification of channel elements that constitute receptor site-4. This information may be useful in future attempts to mimic the bioactive surface of the toxins for the design of anti-insect selective peptidomimetics.
Bibliographical noteFunding Information:
Support for this research was obtained from the United States-Israel Binational Agricultural Research and Development Grants IS-3480-03 and IS-3480-03 (M.G. and D.G.); by the Israeli Science Foundation, Grants 733/01 (M.G.) and 1008/05 (D.G.); and by a grant from the G.I.F., the German–Israeli Foundation for Scientific Research and Development No. G-770-242.1/2002 (D.G. and W.S.).
- Receptor site-4
- Scorpion β-toxins
- Structure-function relationship
- Voltage sensor trapping
- Voltage-gated sodium channels
ASJC Scopus subject areas