title: Contribution of the Tyr-1 in Plantaricin149a to disrupt phospholipid model membranes.
abstract: Plantaricin149a (Pln149a) is a cationic antimicrobial peptide, which was suggested to cause membrane destabilization via the carpet mechanism. The mode of action proposed to this antimicrobial peptide describes the induction of an amphipathic α-helix from Ala7 to Lys20, while the N-terminus residues remain in a coil conformation after binding. To better investigate this assumption, the purpose of this study was to determine the contributions of the Tyr1 in Pln149a in the binding to model membranes to promote its destabilization. The Tyr to Ser substitution increased the dissociation constant (KD) of the antimicrobial peptide from the liposomes (approximately three-fold higher), and decreased the enthalpy of binding to anionic vesicles from -17.2 kcal/mol to -10.2 kcal/mol. The peptide adsorption/incorporation into the negatively charged lipid vesicles was less effective with the Tyr1 substitution and peptide Pln149a perturbed the liposome integrity more than the analog, Pln149S. Taken together, the peptide-lipid interactions that govern the Pln149a antimicrobial activity are found not only in the amphipathic helix, but also in the N-terminus residues, which take part in enthalpic contributions due to the allocation at a lipid-aqueous interface.
authors.affiliation: Institute of Physics of Sao Carlos, University of Sao Paulo, Av. Trabalhador Saocarlense 400, Sao Carlos, SP 13560-970, Brazil. leila@ifsc.usp.br.
authors.forename: José L S
authors.initials: JL
authors.lastname: Lopes
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Gómara
authors.forename: Isabel
authors.initials: I
authors.lastname: Haro
authors.forename: Georgina
authors.initials: G
authors.lastname: Tonarelli
authors.forename: Leila M
authors.initials: LM
authors.lastname: Beltramini
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology; D001430:Bacteriocins / Q000737:chemistry*; D002151:Calorimetry; D002942:Circular Dichroism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009281:Naphthalenes / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011726:Pyridinium Compounds / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014364:Tryptophan; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D001430:Bacteriocins; D008081:Liposomes; D009281:Naphthalenes; D010455:Peptides; D010715:Phosphatidylglycerols; D010743:Phospholipids; D011726:Pyridinium Compounds; C519206:plantaricin 149; C046466:N,N'-4-xylylenebis(pyridinium); D014443:Tyrosine; D014364:Tryptophan; C046465:8-amino-1,3,6-naphthalenetrisulfonic acid; C030345:1,2-dipalmitoylphosphatidylglycerol