Effects of salt and denaturant on structure of the amino terminal alpha-helical segment of an antibacterial peptide dermaseptin and its binding to model membranes

The amino terminal 1-18 domain of dermaseptin s is an important determinant of its structure as well as the antibacterial activity. A thorough investi gation on the structure of the 18-residue peptide (D18) and its binding to model membranes in presence of salt and denaturant guanidinium chloride has been carried out. In presence of salt, there is an increase in the fractio n of peptide molecules in helical conformation. In presence of the denatura nt, D18 is unordered, but addition of the structure-promoting solvent trifl uoroethanol results in a transition to the helical conformation. In presenc e of denaturant, the peptide is unordered, but binding to lipid vesicles is not abolished. Investigation of model membrane permeabilizing ability of t he peptide in solutions containing various proportions of sodium chloride a nd guanidinium chloride indicates that vesicle permeabilization parallels e xtent of binding. The peptide thus binds to lipid vesicles in an unfolded s tate. Since the peptide has propensity to fold into a helical conformation, lipid induced transition to a helical structure occurs, followed by membra ne permeabilization as a result of pore formation.