The efficacy of trivalent cyclic hexapeptides to induce lipid clustering in PG/PE membranes correlates with their antimicrobial activity.
Various models have been proposed for the sequence of events occurring after binding of specific antimicrobial peptides to lipid membranes. The lipid clustering model arose by the finding that antimicrobial peptides can induce a segregation of certain negatively charged lipids in lipid model membranes. Anionic lipid segregation by cationic peptides is initially an effect of charge interaction where the ratio of peptide and lipid charges is thought to be the decisive parameter in the peptide induced lipid demixing. However, the sequence of events following this initial lipid clustering is more complex and can lead to deactivation of membrane proteins involved in cell division or perturbation of lipid reorganization essential for cell division. In this study we used DSC and ITC techniques to investigate the effect of binding different cyclic hexapeptides with varying antimicrobial efficacy, to phosphatidylglycerol (PG)/phosphatidylethanolamine (PE) lipid membranes and their ability to induce lipid segregation in these mixtures. We found that these cyclic hexapeptides consisting of three charged and three aromatic amino acids showed indeed different abilities to induce lipid demixing depending on their amino acid composition and their sequence. The results clearly showed that the cationic amino acids are essential for electrostatic binding but that the three hydrophobic amino acids in the peptides and their position in the sequence also contribute to binding affinity and to the extent of induction of lipid clustering. The efficacy of these different hexapeptides to induce PG clusters in PG/PE membranes was found to be correlated with their antimicrobial activity.
['Finger|Sebastian|S|', 'Kerth|Andreas|A|', 'Dathe|Margitta|M|', 'Blume|Alfred|A|']
D000595:Amino Acid Sequence D023181:Antimicrobial Cationic Peptides D002151:Calorimetry D002152:Calorimetry, Differential Scanning D002462:Cell Membrane D057927:Hydrophobic and Hydrophilic Interactions D008563:Membrane Lipids D009842:Oligopeptides D010456:Peptides, Cyclic D010714:Phosphatidylethanolamines D010715:Phosphatidylglycerols D011485:Protein Binding D013696:Temperature D013816:Thermodynamics
Lipid clustering Antimicrobial peptides Model membranes Differential scanning calorimetry Isothermal titration calorimetry Lipid-peptide interactions