title: Evaluation of the membrane lipid selectivity of the pea defensin Psd1.
abstract: Psd1, a 46 amino acid residues defensin isolated from the pea Pisum sativum seeds, exhibits anti-fungal activity by a poorly understood mechanism of action. In this work, the interaction of Psd1 with biomembrane model systems of different lipid compositions was assessed by fluorescence spectroscopy. Partition studies showed a marked lipid selectivity of this antimicrobial peptide (AMP) toward lipid membranes containing ergosterol (the main sterol in fungal membranes) or specific glycosphingolipid components, with partition coefficients (K(p)) reaching uncommonly high values of 10(6). By the opposite, Psd1 does not partition to cholesterol-enriched lipid bilayers, such as mammalian cell membranes. The Psd1 mutants His36Lys and Gly12Glu present a membrane affinity loss relative to the wild type. Fluorescence quenching data obtained using acrylamide and membrane probes further clarify the mechanism of action of this peptide at the molecular level, pointing out the potential therapeutic use of Psd1 as a natural antimycotic agent.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Gonçalves
authors.forename: Alexandre
authors.initials: A
authors.lastname: Teixeira
authors.forename: João
authors.initials: J
authors.lastname: Abade
authors.forename: Luciano Neves
authors.initials: LN
authors.lastname: de Medeiros
authors.forename: Eleonora
authors.initials: E
authors.lastname: Kurtenbach
authors.forename: Nuno C
authors.initials: NC
authors.lastname: Santos
mesh_terms: D019943:Amino Acid Substitution; D000935:Antifungal Agents / Q000737:chemistry* / Q000378:metabolism; D023082:Defensins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D020125:Mutation, Missense; D018532:Pisum sativum / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D023082:Defensins; D008051:Lipid Bilayers; D010940:Plant Proteins; C410643:defensin 1, Pisum sativum