Membrane interactions of Ocellatins. Where do antimicrobial gaps stem from?
Fiche publication
Date publication
juillet 2021
Journal
Amino acids
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard
Tous les auteurs :
Muñoz-López J, Oliveira JCL, Michel DAGR, Ferreira CS, Neto FG, Salnikov ES, Verly RM, Bechinger B, Resende JM
Lien Pubmed
Résumé
The antimicrobial peptides Ocellatin-LB1, -LB2 and -F1, isolated from frogs, are identical from residue 1 to 22, which correspond to the -LB1 sequence, whereas -LB2 carries an extra N and -F1 additional NKL residues at their C-termini. Despite the similar sequences, previous investigations showed different spectra of activities and biophysical investigations indicated a direct correlation between both membrane-disruptive properties and activities, i.e., ocellatin-F1 > ocellatin-LB1 > ocellatin-LB2. This study presents experimental evidence as well as results from theoretical studies that contribute to a deeper understanding on how these peptides exert their antimicrobial activities and how small differences in the amino acid composition and their secondary structure can be correlated to these activity gaps. Solid-state NMR experiments allied to the simulation of anisotropic NMR parameters allowed the determination of the membrane topologies of these ocellatins. Interestingly, the extra Asn residue at the Ocellatin-LB2 C-terminus results in increased topological flexibility, which is mainly related to wobbling of the helix main axis as noticed by molecular dynamics simulations. Binding kinetics and thermodynamics of the interactions have also been assessed by Surface Plasmon Resonance and Isothermal Titration Calorimetry. Therefore, these investigations allowed to understand in atomic detail the relationships between peptide structure and membrane topology, which are in tune within the series -F1 > > -LB1 ≥ -LB2, as well as how peptide dynamics can affect membrane topology, insertion and binding.
Mots clés
Amphipathic peptide, Antimicrobial peptides, Membrane peptide dynamics, Ocellatins, Peptide–membrane interactions, Solid-state NMR spectroscopy
Référence
Amino Acids. 2021 Jul 12;: