Magainin 2 channel formation in planar lipid membranes: the role of lipid polar groups and ergosterol.
Magainin 2, a polycationic peptide, displays bactericidal and tumoricidal activity, presumably interacting with negatively charged phospholipids in the membrane hosts. In this work, we investigate the role played by the lipid head-group in the interactions and self-association of magainin 2 during pore formation in lipid bilayers. Two methods are used: single-channel and macroscopic incorporation into planar lipid membranes. Single-channel incorporation showed that magainin 2 did not interact with zwitterionic membranes, while the addition of negatively charged dioleoylphosphatidylglycerol to the membrane leads to channel formation. On the other hand, magainin 2 did not form channels in membranes made up of dioleoylphosphatidylserine (DOPS), although the addition of ergosterol to DOPS membranes leads to channel formation. This finding could indicate that ergosterol may be a possible target of magainin 2 in fungal membranes. Further support for this hypothesis comes from experiments in which the addition of ergosterol to palmitoyloleoylphosphatidylcholine membranes induced channel formation. Besides the role of negatively charged membranes, this study has shown that magainin 2 also forms channels in membranes lacking heads, such as monoolein and oxidized cholesterol, indicating an interaction of magainin 2 with acyl chains and cholesterol, respectively. This finding provides further evidence that peptide binding and assembly in lipid membranes is a complex process driven by electrostatic and/or hydrophobic interactions, depending on the structure of the peptide and the membrane composition.
Gallucci
Enrico
E
Dipartimento Farmaco-Biologico, Università degli Studi di Bari, 70126 Bari, Italy. gallucci@farmbiol.uniba.it
Meleleo
Daniela
D
Micelli
Silvia
S
Picciarelli
Vittorio
V
D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D004553:Electric Conductivity; D004563:Electrochemistry / Q000379:methods; D004875:Ergosterol / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D007473:Ion Channels / Q000138:chemical synthesis / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D054806:Magainins; D008564:Membrane Potentials; D008567:Membranes, Artificial; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry*; D016062:Porosity; D055672:Static Electricity; D029867:Xenopus Proteins
D023181:Antimicrobial Cationic Peptides; D007473:Ion Channels; D008051:Lipid Bilayers; D008055:Lipids; D054806:Magainins; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; C042511:1,2-dioleoylphosphatidylserine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; D004875:Ergosterol