Pore formation induced by an antimicrobial peptide: electrostatic effects.
We investigate the mode of action of Cateslytin, an antimicrobial peptide, on zwitterionic biomembranes by performing numerical simulations and electrophysiological measurements on membrane vesicles. Using this natural beta-sheet antimicrobial peptide secreted during stress as a model we show that a single peptide is able to form a stable membrane pore of 1 nm diameter of 0.25 nS conductance found both from calculation and electrical measurements. The resulting structure does not resemble the barrel-stave or carpet models earlier predicted, but is very close to that found in the simulation of alpha-helical peptides. Based on the simulation of a mutated peptide and the effects of small external electric fields, we conclude that electrostatic forces play a crucial role in the process of pore formation.
Jean-François
Frantz
F
UMR 5248, Centre National de la Recherche Scientifique-Université Bordeaux 1, European Institute of Chemistry and Biology, Pessac, France.
Elezgaray
Juan
J
Berson
Pascal
P
Vacher
Pierre
P
Dufourc
Erick J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D053379:Chromogranin A / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D018274:Electroporation; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016062:Porosity / Q000187:drug effects; D017433:Protein Structure, Secondary; D055672:Static Electricity
D023181:Antimicrobial Cationic Peptides; D053379:Chromogranin A; D010446:Peptide Fragments; C527456:chromogranin A (344-358); D004134:Dimyristoylphosphatidylcholine