Membrane-modifying properties of crotamine,a small peptide-toxin from Crotalus durissus terifficus venom |
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Authors: | Michaela Sieber Bettina Bosch Wolfgang Hanke Vera Maura Fernandes de Lima |
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Institution: | 1. University of Hohenheim, Inst. Physiologie, Stuttgart, Germany;2. Departamento de Medicina, Universidade Federal de Sao Joao del Rei, Campus de Divinópolis, Brazil;3. Experimental Surgery Laboratory-LIM 26, School of Medicine, University of Sao Paulo, Brazil |
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Abstract: | BackgroundCrotamine is a small, highly basic myotoxin from the venom of the South American rattlesnake Crotalus durissus terifficus. It is structurally well defined and exhibits some similarities with the β-defensins of vertebrates. An amazing variety of functions and targets that range from analgesia and tumor-related activity to cell penetration have been associated with crotamine. Similar to defensins, it had been argued that crotamine has antimicrobial activity, and this supposition was recently proven. Moreover, it has been argued that the antimicrobial activity of crotamine is due to the membrane permeabilizing properties of the peptide. However, until now, the detailed mechanism of this postulated membrane permeabilization was still unclear.MethodsIn this paper, we used gradient SDS-gels, mass spectroscopy (MALDI-TOF), and monolayer and planar lipid bilayer experiments to investigate the membrane modifying properties of crotamine.ResultsWe showed that crotamine itself forms stable monolayers because of its amphipathic structure, is easily incorporated into lipid monolayers and forms well-defined pores with low cationic selectivity in planar lipid bilayers; these properties might account for the antimicrobial activity of crotamine. The pores are probably oligomeric aggregates of crotamine molecules, as suggested by the tendency of crotamine to form oligomers in aqueous solution and the fact that the structure of crotamine does not allow pore formation by monomers.ConclusionsThe membrane modifying and antimicrobial properties of crotamine are probably due to homo-oligomeric pore formation in membranes.General significanceThe results should be highly interesting to researchers in the fields of biophysics, pharmacology, toxicology and antibiotics. |
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Keywords: | Crotamine Crotalus venom Monolayer Planar lipid bilayer Pore formation Antimicrobial peptides |
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