Multiple states of beta-sheet peptide protegrin in lipid bilayers

Protegrin-1 (PG-1), a beta-sheet antimicrobial peptide, was studied in alig ned lipid bilayers by oriented circular dichroism (OCD), All of its spectra measured in a variety of lipid compositions were linear superpositions of two primary basis spectra, indicating that PG-1 existed in two different st ates in membranes. We designated these as state S and state I. The state as sumed by PG-I was strongly influenced by lipid composition, peptide concent ration, and hydration condition. We have previously reported that the helic al peptides, alamethicin and magainin, also exhibit two distinct OCD basis spectra-one corresponding to surface adsorption with the helix parallel to the bilayer and the other with perpendicular transbilayer insertion. States S and I of PG-1 may correspond to the surface state and the insertion stat e of alamethicin, since they show a similar dependence on lipid composition , peptide concentration, and hydration condition. Nonoriented CD spectra ob tained from vesicle, micelle, and solution preparations are not linear supe rpositions of the basis spectra of the states S and I. This indicates that a molecular orientation change alone is insufficient to describe the S <-> I transition. Rather, a more complicated process is taking place, perhaps i nvolving a change in the hydrogen bonding pattern of the backbone. Although the structural basis of the OCD spectra remains to be determined, the disc overy of two distinct states can provide information about dynamic changes of PG-1 in membranelike environments, properties undoubtedly related to its antimicrobial and cytotoxic effects.