Peptide antibiotic trichogin in model membranes: Self-association and capture of fatty acids

Ekaterina F. Afanasyeva, Victoria N. Syryamina, Marta De Zotti, Fernando Formaggio, Claudio Toniolo, Sergei A. Dzuba

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

The antimicrobial action of peptides in bacterial membranes is commonly related to their mode of self-assembling which results in pore formation. To optimize peptide antibiotic use for therapeutic purposes, a study on the concentration dependence of self-assembling process is thus desirable. In this work, we investigate this dependence for peptaibol trichogin GA IV (Tric) in the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) model membrane in the range of peptide concentrations between 0.5 and 3.3 mol%. Pulsed double electron-electron resonance (PELDOR) applied on spin-labeled peptide analogs highlights the onset of peptide dimerization above a critical peptide concentration value, namely ~ 2 mol%. Electron spin echo (ESE) envelope modulation (ESEEM) for D2O-hydrated bilayers shows that dimerization is accompanied by peptide re-orientation towards a trans-membrane disposition. For spin-labeled stearic acids (5-DSA) in POPC bilayers, the study of ESE decays and ESEEM in the presence of a deuterated peptide analog indicates that above the critical peptide concentration the 5-DSA molecules are attracted by peptide molecules, forming nanoclusters. As the 5-DSA molecules represent a model for the behavior of fatty acids participating in bacterial membrane homeostasis, such capturing action by Tric may represent an additional mechanism of its antibiotic activity.

Original languageEnglish
Pages (from-to)524-531
Number of pages8
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1861
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

Keywords

  • Dipolar spectroscopy
  • EPR
  • ESEEM
  • Fatty acids
  • Ion channels
  • PELDOR
  • Trichogin
  • LIPOPEPTAIBOL
  • WATER CONCENTRATION
  • CHOLESTEROL
  • GA-IV
  • ANTIMICROBIAL PEPTIDES
  • ALAMETHICIN
  • ORIENTATION
  • SPIN LABELS
  • AGGREGATION
  • Anti-Bacterial Agents/pharmacology
  • Peptides/pharmacology
  • Dimerization
  • Amino Acid Sequence
  • Electron Spin Resonance Spectroscopy
  • Stearic Acids/chemistry
  • Lipopeptides/pharmacology
  • Water/chemistry
  • Lipid Bilayers/chemistry
  • Phosphatidylcholines/chemistry
  • Fatty Acids/chemistry

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