title: Membrane perturbation by the antimicrobial peptide PMAP-23: a fluorescence and molecular dynamics study.
abstract: Several bioactive peptides exert their biological function by interacting with cellular membranes. Structural data on their location inside lipid bilayers are thus essential for a detailed understanding of their mechanism of action. We propose here a combined approach in which fluorescence spectroscopy and molecular dynamics (MD) simulations were applied to investigate the mechanism of membrane perturbation by the antimicrobial peptide PMAP-23. Fluorescence spectra, depth-dependent quenching experiments, and peptide-translocation assays were employed to determine the location of the peptide inside the membrane. MD simulations were performed starting from a random mixture of water, lipids and peptide, and following the spontaneous self-assembly of the bilayer. Both experimental and theoretical data indicated a peptide location just below the polar headgroups of the membrane, with an orientation essentially parallel to the bilayer plane. These findings, together with experimental results on peptide-induced leakage from large and giant vesicles, lipid flip-flop and peptide exchange between vesicles, support a mechanism of action consistent with the "carpet" model. Furthermore, the atomic detail provided by the simulations suggested the occurrence of an additional, more specific and novel mechanism of bilayer destabilization by PMAP-23, involving the unusual insertion of charged side chains into the hydrophobic core of the membrane.
authors.affiliation: Dipartimento di Scienze e Tecnologie Chimiche, Università di Roma Tor Vergata, Via della Ricerca Scientifica 1 00133 Roma, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Orioni
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Bocchinfuso
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Antonio
authors.initials: A
authors.lastname: Palleschi
authors.forename: Giacinto
authors.initials: G
authors.lastname: Grande
authors.forename: Sara
authors.initials: S
authors.lastname: Bobone
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Park
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Kyung-soo
authors.initials: KS
authors.lastname: Hahm
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Stella
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D005453:Fluorescence; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D053835:Unilamellar Liposomes; C086301:porcine myeloid antibacterial peptide 23