title: Controls and constrains of the membrane disrupting action of Aurein 1.2.
abstract: Aurein 1.2 is a 13 residue antimicrobial peptide secreted by the Australian tree frog Litoria Aurea. It is a surface-acting membrane disrupting peptide that permeabilizes bacterial membranes via the carpet mechanism; the molecular details of this process are mostly unknown. Here the mechanism of action of Aurein 1.2 was investigated with an emphasis on the role of membrane charge and C-terminal amidation of the peptide. Using quartz crystal microbalance (QCM) fingerprinting it was found that the membrane charge correlates with membrane affinity of the peptide, however the binding and the membrane disrupting processes are not charge driven; increased membrane charge reduces the membrane disrupting activity. Coarse grain simulations revealed that phenylalanine residues act as membrane anchors. Accordingly Aurein 1.2 has the ability to bind to any membrane. Furthermore, bundling precludes membrane disruption in case of wild type peptides, while non C-terminal amidated peptides form random aggregates leading to detachment from the membrane. Hence C-terminal amidation is crucial for Aurein 1.2 action. Our results suggest that Aurein 1.2 acts via aggregation driven membrane penetration. The concomitant change in the tension of the outer leaflet imposes a spontaneous curvature on the membrane, leading to disintegration.
authors.affiliation: Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora Vic 3086, Australia.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Shahmiri
authors.affiliation: Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora Vic 3086, Australia.
authors.forename: Marta
authors.initials: M
authors.lastname: Enciso
authors.affiliation: Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora Vic 3086, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Mechler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D058525:Quartz Crystal Microbalance Techniques; D011898:Ranidae / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; C506635:aurein 1.2 peptide