Fluorescence and circular dichroism study of the interaction between indolicidin, a tryptophan-rich antimicrobial peptide, and model membranes

摘要

We have examined the interaction of the antimicrobial peptide indolicidin (IND) with large unilamellar vesicles of the zwitter-ionic phospholipid 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) and of 2:1 mixtures of POPC and negatively charged 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG). We also investigated the interaction between IND and lysophosphatidylcholine (LPC) and LPC-lysophosphatidylglycerol (LPG) (2:1) micelles. The peptide's fluorescence intensity increased and the wavelength of maximum emission decreased upon binding to all model membrane systems. IND's binding to zwitterionic interfaces indicates the contribution of hydrophobic interactions. The stronger binding to POPGPOPG (2:1) than to pure POPC evinced the contribution of electrostatic interactions. Fluores- cence quenching studies with 2,2,6, 6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid (TOAC) suggest that IND resides in the water-bilayer interface region in vesicles and in LPC-LPG (2:1) micelles, being more deeply inserted in LPC micelles. IND's pH titration is drastically altered in the presence of lipid, probably due to pK shifts of the side chain residues, resulting from surface charge effects, and to binding-induced conformational changes. Circular dichroism spectra corroborate the conclusion that binding to model membranes induces peptide conformational changes.