Synthetic peptides that reproduce the N-terminus of sticholysins as models for the study of their structure-function relationship
Abstract
The Caribbean Sea anemone Stichodactyla helianthus produces two pore-forming proteins, sticholysins I and II (StI and StII). To clarify the contribution of the first thirty (StII) or thirty-one (StI) N-terminal amino acid residues to the activity of the toxins, four peptides spanning residues 1-31 of StI (StI1-31, StI12-31) and 1-30 of StII (StII1-30, StII11-30) were synthesized. StII1-30 was the most active peptide, followed by StI1-31 and the shortest ones. The difference between the hemolytic activities of the largest peptides qualitatively reproduces that found between the respective toxins StI and StII. The results suggest the importance of continuity of the 1-10 hydrophobic amino acid sequence in StII1-30 for displaying higher membrane binding and activity. Thus, the different peptide membranotropic action is explained in terms of the differences in their hydrophobic and electrostatic properties. Furthermore, we also demonstrated that StII1-30 forms pores of similar radius to that of the protein (around 1 nm), with its N-terminus oriented towards the hydrophobic core of the bilayer while the rest of the peptide is more exposed to the aqueous environment, as hypothesized for sticholysins. Altogether these results demonstrate that synthetic peptides that reproduce sticholysins' N-terminus are not only a good model of these toxins structure and function but, and due to its reduced molecular size, could also be useful biotechnological tools instead of their larger parental proteins. This research won the 2012 Award of the Cuban National Academy of Sciences.
