TY - JOUR

T1 - Tylopeptin B peptide antibiotic in lipid membranes at low concentrations

T2 - Self-assembling, mutual repulsion and localization

AU - Syryamina, Victoria N.

AU - Sannikova, Natalia E.

AU - De Zotti, Marta

AU - Gobbo, Marina

AU - Formaggio, Fernando

AU - Dzuba, Sergei A.

N1 - Funding Information: VNS and SAD acknowledge support from the Russian Science Foundation, project No. 15-15-00021. MDZ gratefully acknowledges the Italian Ministry of Education, University and Research (MIUR), grant number PRIN 20173LBZM2, and the University of Padova (Italy), grant number P-DiSC#04BIRD2019-UNIPD for funding. Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - The medium-length peptide Tylopeptin B possesses activity against Gram-positive bacteria. It binds to bacterial membranes altering their mechanical properties and increasing their permeability. This action is commonly related with peptide self-assembling, resulting in the formation of membrane channels. Here, pulsed double electron-electron resonance (DEER) data for spin-labeled Tylopeptin B in palmitoyl-oleoyl-glycero-phosphocholine (POPC) model membrane reveal that peptide self-assembling starts at concentration as low as 0.1 mol%; above 0.2 mol% it attains a saturation-like dependence with a mean number of peptides in the cluster = 3.3. Using the electron spin echo envelope modulation (ESEEM) technique, Tylopeptin B molecules are found to possess a planar orientation in the membrane. In the peptide concentration range between 0.1 and 0.2 mol%, DEER data show that the peptide clusters have tendency of mutual repulsion, with a circle of inaccessibility of radius around 20 nm. It may be proposed that within this radius the peptides destabilize the membrane, providing so the peptide antimicrobial activity. Exploiting spin-labeled stearic acids as a model for free fatty acids (FFA), we found that at concentrations of 0.1–0.2 mol% the peptide promotes formation of lipid-mediated FFA clusters; further increase in peptide concentration results in dissipation of these clusters.

AB - The medium-length peptide Tylopeptin B possesses activity against Gram-positive bacteria. It binds to bacterial membranes altering their mechanical properties and increasing their permeability. This action is commonly related with peptide self-assembling, resulting in the formation of membrane channels. Here, pulsed double electron-electron resonance (DEER) data for spin-labeled Tylopeptin B in palmitoyl-oleoyl-glycero-phosphocholine (POPC) model membrane reveal that peptide self-assembling starts at concentration as low as 0.1 mol%; above 0.2 mol% it attains a saturation-like dependence with a mean number of peptides in the cluster = 3.3. Using the electron spin echo envelope modulation (ESEEM) technique, Tylopeptin B molecules are found to possess a planar orientation in the membrane. In the peptide concentration range between 0.1 and 0.2 mol%, DEER data show that the peptide clusters have tendency of mutual repulsion, with a circle of inaccessibility of radius around 20 nm. It may be proposed that within this radius the peptides destabilize the membrane, providing so the peptide antimicrobial activity. Exploiting spin-labeled stearic acids as a model for free fatty acids (FFA), we found that at concentrations of 0.1–0.2 mol% the peptide promotes formation of lipid-mediated FFA clusters; further increase in peptide concentration results in dissipation of these clusters.

KW - DEER

KW - EPR

KW - ESEEM

KW - Free fatty acids

KW - Peptide-lipid interactions

KW - Spin labels

UR - http://www.scopus.com/inward/record.url?scp=85101694830&partnerID=8YFLogxK

U2 - 10.1016/j.bbamem.2021.183585

DO - 10.1016/j.bbamem.2021.183585

M3 - Article

C2 - 33640429

AN - SCOPUS:85101694830

VL - 1863

JO - Biochimica et Biophysica Acta - Biomembranes

JF - Biochimica et Biophysica Acta - Biomembranes

SN - 0005-2736

IS - 9

M1 - 183585

ER -