Effect of Head Group and Curvature on Binding of the Antimicrobial Peptide Tritrpticin to Lipid Membranes

Abstract

Experimental studies revealed that the N-terminal (1-18) fragment is responsible for the activity of the whole peptide, with a negligible toxicity towards eukaryotic cells, thus representing an excellent canditate for future applications. It is expected, like most of the known AMPs, to target the bacterial plasmamembrane but its 3D-structure and detailed mode of action are still unknown. Before an in-depth investigation on peptide/membranes interactions could be undertaken, it is necessary to characterize its folding propensity in solution, in order to understand what is intrinsically due to the peptide sequence and what is actually driven by the membrane interaction. In this scenario, the present study represents the first structural investigation on Esculentin-1b(1-18). Liquid state NMR was employed to determine the peptide structure, moving from water to increasing amounts of trifluorethanol. NMR parameters have been used as restraints during structure determination through a simulated annealing procedure. The results showed that Esculentin-1b(1-18) has a clear tendency to fold in a helical conformation with increasing the environment hydrophobicity, confirming circular dichroism data. Interestingly, the helix is formed only for residues ranging from 3 to 11, while it appears to be unstructured in the rest of the peptide. Nevertheless, the whole conformation was found to be amphipathic with a 3-mer hydrophobic cluster right in the middle of the unstructured segment, which might act as an anchoring tail upon membrane binding.