Membrane thinning effect of the beta-sheet antimicrobial protegrin

Lipid bilayers containing the antimicrobial peptide protegrin-1 (PG-1) were studied by lamellar X-ray diffraction. Previously, we have shown that the peptide exists in two distinct states when associated with lipid bilayers d epending on the peptide concentration [Heller, W. T., Waring, A. J., Lehrer , R. I., and Huang, H. W. (1998) Biochemistry 37, 17331-17338]. For concent rations below a lipid-dependent threshold, PG-1 exhibits a unique oriented circular dichroism spectrum called the S state. X-ray experiments show that in this state PG-1 decreases the thickness of the lipid bilayer in proport ion to the peptide concentration, similar to alamethicin's membrane thinnin g effect. This indicates that the S state is adsorbed in the headgroup regi on of the lipid bilayer, where the peptide is in an inactive state. For PG- I above the threshold concentration, X-ray diffraction shows that the inter action between the peptide and the bilayer changes significantly. These res ults suggest that PG-1 has the same concentration-gated mechanism of action as alamethicin.