High-resolution structural profile of hylaseptin-4: Aggregation, membrane topology and pH dependence of overall membrane binding process.
Fiche publication
Date publication
février 2021
Journal
Biochimica et biophysica acta. Biomembranes
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard
Tous les auteurs :
Nunes LO, Munhoz VHO, Sousa AA, de Souza KR, Santos TL, Bemquerer MP, Ferreira DEC, de Magalhães MTQ, Resende JM, Alcântara AFC, Aisenbrey C, Veloso DP, Bechinger B, Verly RM
Lien Pubmed
Résumé
Hylaseptin-4 (HSP-4, GIGDILKNLAKAAGKAALHAVGESL-NH) is an antimicrobial peptide originally isolated from Hypsiboas punctatus tree frog. The peptide has been chemically synthetized for structural investigations by CD and NMR spectroscopies. CD experiments reveal the high helical content of HSP-4 in biomimetic media. Interestingly, the aggregation process seems to occur at high peptide concentrations either in aqueous solution or in presence of biomimetic membranes, indicating an increase in the propensity of the peptide for adopting a helical conformation. High-resolution NMR structures determined in presence of DPC-d micelles show a highly ordered α-helix from amino acid residues I2 to S24 and a smooth bend near G14. A large separation between hydrophobic and hydrophilic residues occurs up to the A16 residue, from which a shift in the amphipathicity is noticed. Oriented solid-state NMR spectroscopy show a roughly parallel orientation of the helical structure along the POPC lipid bilayer surface, with an insertion of the hydrophobic N-terminus into the bilayer core. Moreover, a noticeable pH dependence of the aggregation process in both aqueous and in biomimetic membrane environments is attributed to a single histidine residue (H19). The protonation degree of the imidazole side-chain might help in modulating the peptide-peptide or peptide-lipid interactions. Finally, molecular dynamics simulations confirm the orientation and preferential helical conformation and in addition, show that HSP-4 tends to self-aggregate in order to stabilize its active conformation in aqueous or phospholipid bilayer environments.
Mots clés
Aggregation process, Antimicrobial mechanism of action, Biophysical prediction of peptidemembrane interactions, Conformational analysis of peptides, Membrane active peptides, Peptide-membrane interaction
Référence
Biochim Biophys Acta Biomembr. 2021 Feb 5;:183581