| Title: | Structure and mode of action of the membrane-permeabilizing antimicrobial peptide pheromone plantaricin A |
| Author(s): | Kristiansen PE; Fimland G; Mantzilas D; Nissen-Meyer J; |
| Address: | "Department of Molecular Biosciences, University of Oslo, Norway. eugen@kjemi.uio.no" |
| ISSN/ISBN: | 0021-9258 (Print) 0021-9258 (Linking) |
| Abstract: | "The three-dimensional structure in dodecyl phosphocholine micelles of the 26-mer membrane-permeabilizing bacteriocin-like pheromone plantaricin A (PlnA) has been determined by use of nuclear magnetic resonance spectroscopy. The peptide was unstructured in water but became partly structured upon exposure to micelles. An amphiphilic alpha-helix stretching from residue 12 to 21 (possibly also including residues 22 and 23) was then formed in the C-terminal part of the peptide, whereas the N-terminal part remained largely unstructured. PlnA exerted its membrane-permeabilizing antimicrobial activity through a nonchiral interaction with the target cell membrane because the d-enantiomeric form had the same activity as the natural l-form. This nonchiral interaction involved the amphiphilic alpha-helical region in the C-terminal half of PlnA because a 17-mer fragment that contains the amphiphilic alpha-helical part of the peptide had antimicrobial potency that was similar to that of the l- and d-enantiomeric forms of PlnA. Also the pheromone activity of PlnA depended on this nonchiral interaction because both the l- and d-enantiomeric forms of the 17-mer fragment inhibited the pheromone activity. The pheromone activity also involved, however, a chiral interaction between the N-terminal part of PlnA and its receptor because high concentrations of the l-form (but not the d-form) of a 5-mer fragment derived from the N-terminal part of PlnA had pheromone activity. The results thus reveal a novel mechanism whereby peptide pheromones such as PlnA may function. An initial nonchiral interaction with membrane lipids induces alpha-helical structuring in a segment of the peptide pheromone. The peptide becomes thereby sufficiently structured and properly positioned in the membrane interface, thus enabling it to engage in a chiral interaction with its receptor in or near the membrane water interface. This membrane-interacting mode of action explains why some peptide pheromones/hormones such as PlnA sometimes display antimicrobial activity in addition to their pheromone activity" |
| Keywords: | "Amino Acid Sequence Bacteriocins/*chemistry/pharmacology Cell Membrane/drug effects/metabolism Circular Dichroism Lactobacillus/metabolism Lipids/chemistry Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Peptides/chemistry Pherom;" |
| Notes: | "MedlineKristiansen, Per Eugen Fimland, Gunnar Mantzilas, Dimitris Nissen-Meyer, Jon eng Research Support, Non-U.S. Gov't 2005/04/05 J Biol Chem. 2005 Jun 17; 280(24):22945-50. doi: 10.1074/jbc.M501620200. Epub 2005 Apr 1" |
