beta/delta-Agatoxins are unique modulators of voltage-gated sodium channels
(2010) 35th Congress of the Federation-of-European-Biochemical-Societies — Location: Gothenburg(Sweden) (26.June.2010)
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- Abstract
- Search of natural polypeptide molecules that affect the nervous systems of humans and animals with high selectivity and efficiency is one of the most important tasks of modern biochemistry and therefore has practical value to pharmacy, medicine and biotechnology. This work is devoted to identification and investigation of a new family of peptide components from Agelena orientalis (Agelenidae) spider venom designated b/d-agatoxins that modulate the activity of insect sodium channels. Complete amino acid sequences of all peptides (36– 38 residues) were established by automated Edman degradation. Purified toxins are characterized by a high degree of similarity with each other (up to 97%) and with some other toxins such as l-agatoxins, curtatoxins and d-palutoxins. b/d-Agatoxins were tested on Xenopus laevis oocytes expressing genes of insect sodium channel proteins using the two-electrode voltage clamp technique. Application of all studied compounds at concentrations of ~ 100 nM evoked a modulating effect on the fruit fly Drosophila melanogaster voltage-gated sodium channels (DmNav1), i.e. inhibition of inactivation (the socalled a-effect) and a shift of channel activation voltage dependence (b-effect). This peculiar ‘double’ effect of polypeptide toxins on sodium channels can be used for structure and function investigations. Moreover, b/d-agatoxins are characterized by a high specificity towards channels of insects, being totally ineffective on their mammalian counterparts. Such selectivity of the peptides provides a basis for creating new highly effective and safe insecticides.
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Nikolsky, A., Billen, B., Vassilevski, A., Tytgat, J., & Grishin, E. (2010). beta/delta-Agatoxins are unique modulators of voltage-gated sodium channels. FEBS Journal, 277, 292-293. https://hdl.handle.net/2078.5/43261 (Original work published 2010)