title: Molecular electroporation: a unifying concept for the description of membrane pore formation by antibacterial peptides, exemplified with NK-lysin.
abstract: The antibacterial activity of many small, positively charged peptides and proteins is based on pore formation in lipid bilayers. It is here proposed to arise from an electroporation effect. This hypothesis is supported by calculations of the electrostatic potential of NK-lysin associated to a membrane. For a significant area of the protein-membrane interface, the electrostatic potential is found to be above the minimum threshold for electroporation. A single highly charged alpha-helical segment of NK-lysin is mainly responsible for this effect. It is experimentally demonstrated that a peptide comprising this helix has antibacterial activity. We propose that superficial association to membranes suffices to trigger electroporation, provided the peptide is sufficiently charged. The effect is referred to as molecular electroporation.
authors.affiliation: Department of Bioscience at Novum, Karolinska Institutet, 141 57, Huddinge, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Miteva
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: A
authors.initials: A
authors.lastname: Karshikoff
authors.forename: G
authors.initials: G
authors.lastname: Otting
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D018274:Electroporation; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology; D008561:Membrane Fusion; D008564:Membrane Potentials; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000737:chemistry / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000494:pharmacology*; D055672:Static Electricity
chemical_list: D000900:Anti-Bacterial Agents; C093238:NK-lysin; D011510:Proteolipids; D011663:Pulmonary Surfactants