Trichogin GA IV alignment and oligomerization in phospholipid bilayers.
Fiche publication
Date publication
mai 2019
Journal
Chembiochem : a European journal of chemical biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard
Tous les auteurs :
Salnikov ES, De Zotti M, Bobone S, Mazzuca C, Raya J, Siano AS, Peggion C, Toniolo C, Stella L, Bechinger B
Lien Pubmed
Résumé
Trichogin GA IV is a short peptaibol with antimicrobial activity. This uncharged but amphipathic sequence is aligned at the membrane interface and undergoes a transition to an aggregated state that inserts more deeply into the membrane, an assembly which predominates at P/L 1/20. Here, the natural trichogin sequence was prepared and reconstituted into oriented lipid bilayers. The resulting 15N chemical shift is indicative of a well-defined alignment of the peptide parallel to the membrane surface at peptide-to-lipid ratios of 1/120 and 1/20. When the peptide concentration is increased to 1/8 an additional peptide topology is observed indicative of a heterogeneous orientation, with helix alignments ranging from around the magic angle to perfectly in-plane. The topological preference of the trichogin helix for an orientation parallel to the membrane surface is confirmed by ATR FTIR spectroscopy. Furthermore, 19F CODEX experiments were performed on a trichogin sequence carrying 19F-Phe at position 10. The CODEX decay is in agreement with a tetrameric complex, where the 19F sites are about 9 - 9.5 Å apart. Thus, a model emerges where the monomeric peptide aligns along the membrane surface. When the peptide concentration increases, first dimeric and thereafter tetrameric assemblies form, made up from helices oriented predominantly parallel to the membrane surface. Formation of these aggregates correlates with the release of vesicle contents including relatively large molecules.
Mots clés
helix topology, membrane permeabilization, oligomer size and structure, peptaibol, supported lipid bilayers
Référence
Chembiochem. 2019 May 24;: