Secondary Structure and Membrane Interaction of PR‐39, a Pro+Arg‐rich Antibacterial Peptide

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Abstract
PR‐39 is a 4719‐Da peptide isolated from pig intestine and belonging to the recently discovered family of Pro + Arg‐rich antibacterial peptides. PR‐39 does not lyse Escherichia coli, instead the lethal action is probably linked to the termination of DNA and protein synthesis [Boman, H. G., Agerberth, B. & Boman, A. (1993) Infect. Immun. 61, 2978–2984].Circular dichroism and Fourier‐transform infrared spectroscopy have been used to investigate the secondary structure of PR‐39 in the absence or presence of lipids. According to the circular dichroic data, this structure is not altered upon incubation of PR‐39 with negatively charged vesicles, although the infrared spectra suggest that the hydrogen bond pattern is modified upon the peptide—lipid interaction. This is detected by a shift in the maximum wavelength of absorption of PR‐39 from 1636 cm−1 in the absence of lipids to 1645 cm−1 in the presence of lipids. We have further addressed the question of the possible mechanism of interaction of PR‐39 with model membranes (liposomes and planar lipid bilayers) whose lipid compositions mimick that of the E. coli inner membrane. PR‐39 induced a calcein release from large unilamellar vesicles, which is dependent upon the peptide concentration and upon the presence of negatively charged lipid (glycerophosphoglycerol) in the membrane. The binding study of PR‐39 to dioleoylglycerophosphoglycerol vesicles suggests that nearly 100% of the added peptide is membrane‐bound. Addition of PR‐39 to a planar lipid bilayer induced a linear increase in the current but no channel formation was observed since no discrete steps of conductance occurred.