TY - JOUR

T1 - Peptide antibiotic trichogin in model membranes

T2 - Self-association and capture of fatty acids

AU - Afanasyeva, Ekaterina F.

AU - Syryamina, Victoria N.

AU - De Zotti, Marta

AU - Formaggio, Fernando

AU - Toniolo, Claudio

AU - Dzuba, Sergei A.

N1 - Copyright © 2018 Elsevier B.V. All rights reserved.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

KW - Dipolar spectroscopy

KW - EPR

KW - ESEEM

KW - Fatty acids

KW - Ion channels

KW - PELDOR

KW - Trichogin

KW - LIPOPEPTAIBOL

KW - WATER CONCENTRATION

KW - CHOLESTEROL

KW - GA-IV

KW - ANTIMICROBIAL PEPTIDES

KW - ALAMETHICIN

KW - ORIENTATION

KW - SPIN LABELS

KW - AGGREGATION

KW - Anti-Bacterial Agents/pharmacology

KW - Peptides/pharmacology

KW - Dimerization

KW - Amino Acid Sequence

KW - Electron Spin Resonance Spectroscopy

KW - Stearic Acids/chemistry

KW - Lipopeptides/pharmacology

KW - Water/chemistry

KW - Lipid Bilayers/chemistry

KW - Phosphatidylcholines/chemistry

KW - Fatty Acids/chemistry

UR - http://www.scopus.com/inward/record.url?scp=85058568815&partnerID=8YFLogxK

U2 - 10.1016/j.bbamem.2018.12.006

DO - 10.1016/j.bbamem.2018.12.006

M3 - Article

C2 - 30550880

AN - SCOPUS:85058568815

VL - 1861

SP - 524

EP - 531

JO - Biochimica et Biophysica Acta - Biomembranes

JF - Biochimica et Biophysica Acta - Biomembranes

SN - 0005-2736

IS - 2

ER -