Synthetic fluorescent analogs of the natural lipopeptide trichogin GA IV were used to investigate the peptide position and orientation in model membranes. A translocation assay based on Forster energy transfer indicates that trichogin is associated to both the outer and inner leaflet of the membrane, even at low concentration, when it is not active. Fluorescence quenching measurements, performed by using water soluble quenchers and quenchers positioned in the membrane at different depths, indicate that at low membrane-bound peptide/lipid ratios trichogin lies close to the region of polar headgroups. By increasing peptide concentration until membrane leakage takes place, a cooperative transition occurs and a significant fraction of the peptide becomes deeply buried into the bilayer. Remarkably, this change in peptide position is strictly coupled with peptide aggregation. Therefore, the mechanism of trichogin action can be envisaged as based on a two-state transition controlled by peptide concentration. One state is the monomeric, surface bound and inactive peptide, and the other state is a buried, aggregated form, which is responsible for membrane leakage and bioactivity.

Mazzuca, C., Stella, L., Venanzi, M., Formaggio, F., Toniolo, C., Pispisa, B. (2005). Mechanism of membrane activity of the antibiotic trichogin GA IV: a two-state transition controlled by peptide concentration. BIOPHYSICAL JOURNAL, 88(5), 3411-3421 [10.1529/biophysj.104.056077].

Mechanism of membrane activity of the antibiotic trichogin GA IV: a two-state transition controlled by peptide concentration

MAZZUCA, CLAUDIA;STELLA, LORENZO;VENANZI, MARIANO;PISPISA, BASILIO
2005-05-01

Abstract

Synthetic fluorescent analogs of the natural lipopeptide trichogin GA IV were used to investigate the peptide position and orientation in model membranes. A translocation assay based on Forster energy transfer indicates that trichogin is associated to both the outer and inner leaflet of the membrane, even at low concentration, when it is not active. Fluorescence quenching measurements, performed by using water soluble quenchers and quenchers positioned in the membrane at different depths, indicate that at low membrane-bound peptide/lipid ratios trichogin lies close to the region of polar headgroups. By increasing peptide concentration until membrane leakage takes place, a cooperative transition occurs and a significant fraction of the peptide becomes deeply buried into the bilayer. Remarkably, this change in peptide position is strictly coupled with peptide aggregation. Therefore, the mechanism of trichogin action can be envisaged as based on a two-state transition controlled by peptide concentration. One state is the monomeric, surface bound and inactive peptide, and the other state is a buried, aggregated form, which is responsible for membrane leakage and bioactivity.
mag-2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore CHIM/02 - CHIMICA FISICA
English
Con Impact Factor ISI
Spectroscopy, Fourier Transform Infrared; Membranes; Spectrometry, Fluorescence; Dose-Response Relationship, Drug; Lipids; Lipopeptides; Liposomes; Water; Biophysics; Anti-Bacterial Agents; Macromolecular Substances; Glycopeptides; Lipid Bilayers; Models, Chemical; Peptides; Time Factors; Protein Transport; Antimicrobial Cationic Peptides
Mazzuca, C., Stella, L., Venanzi, M., Formaggio, F., Toniolo, C., Pispisa, B. (2005). Mechanism of membrane activity of the antibiotic trichogin GA IV: a two-state transition controlled by peptide concentration. BIOPHYSICAL JOURNAL, 88(5), 3411-3421 [10.1529/biophysj.104.056077].
Mazzuca, C; Stella, L; Venanzi, M; Formaggio, F; Toniolo, C; Pispisa, B
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/35262
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