The NMR three-dimensional structure of the peptaibol antibiotic longibrachin LGA I - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2000

The NMR three-dimensional structure of the peptaibol antibiotic longibrachin LGA I

Résumé

Longibrachin LGA I is a 20-residue antibiotic peptide produced by the fungus Trichoderma longibrachiatum and belonging to the peptaibol class. It modifies the permeability of membrane bilayers, forming voltage-gated ion channels according to the barrel-stave model, which involves transbilayer aggregates of helical monomers. LGA I differs from the well-known alamethicin F50 (Alm F50) by a single Pro2 - Ala substitution. This naturally occurring sequence modification was used to probe the role of the residue at position 2 in the channel stability, as a significative decrease in the channel lifetimes was observed for LGA I, as compared to Alm F50. The three-dimensional structure of LGA I was thus studied based upon 2D-NMR spectroscopy and molecular modelling. The resonance assignments and conformational parameters (NOEs, 3JNHCalphaH) coupling constants and thermal coefficients of amide protons) were obtained for LGA I in methanol solution. The 3D-structure was calculated using the program X-PLOR starting from 155 NOE-derived interproton distance constraints and 11 phi dihedral angle restraints. A total of 123 converged structures, consistent with the NMR data, were generated by restrained molecular dynamics and energy minimization calculations. LGA I forms a 33 Angstroms long amphipathic helix, mainly alpha-type, apportioned into two segments (1-9 and 14-20) linked by a bend. The bend angle is about 150°. The structure is very close to that of Alm F50, the residue at position 2 occupying the same location in the hydrophilic sector of the helix for both peptides. Shortening of the LGA I channel lifetimes should thus be due to lesser anchoring of the N-terminal part of the helices at the trans-bilayer interface, when position 2 is occupied by alanine, which is considered as more hydrophobic than proline. LGA I: Ac U1-A-U-A-U-A-Q-U-V-U-G-L-U-P-V-U-U-Q-Q-Fol20 U (Aib): α-aminoisobutyric acid; Fol (Pheol): phenylalaninol
Fichier non déposé

Dates et versions

hal-00087884 , version 1 (27-07-2006)

Identifiants

  • HAL Id : hal-00087884 , version 1

Citer

G. Leclerc, M. Cheminant, I. Segalas, A. Blond, J. Peduzzi, et al.. The NMR three-dimensional structure of the peptaibol antibiotic longibrachin LGA I. Peptides 2000, Proceedings 26th European Peptide Symposium, Sep 2000, Montpellier, France. ⟨hal-00087884⟩

Collections

MNHN CNRS
39 Consultations
0 Téléchargements

Partager

Gmail Facebook X LinkedIn More