Membrane interactions of the anuran antimicrobial peptide HSP1-NH2: Different aspects of the association to anionic and zwitterionic biomimetic systems

Studies have suggested that antimicrobial peptides act by different mechanisms, such as micellisation, self-assembly of nanostructures and pore formation on the membrane surface. This work presents an extensive investigation of the membrane interactions of the 14 amino-acid antimicrobial peptide hylaseptin P1-NH2 (HSP1-NH2), derived from the tree-frog Hyla punctata, which has stronger antifungal than antibacterial potential. Biophysical and structural analyses were performed and the correlated results were used to describe in detail the interactions of HSP1-NH2 with zwitterionic and anionic detergent micelles and phospholipid vesicles. HSP1-NH2 presents similar well-defined helical conformations in both zwitterionic and anionic micelles, although NMR spectroscopy revealed important structural differences in the peptide N-terminus. 2H exchange experiments of HSP1-NH2 indicated the insertion of the most N-terminal residues (1–3) in the DPC-d38 micelles. A higher enthalpic contribution was verified for the interaction of the peptide with anionic vesicles in comparison with zwitterionic vesicles. The pore formation ability of HSP1-NH2 (examined by dye release assays) and its effect on the size and surface charge as well as on the lipid acyl chain ordering (evaluated by Fourier-transform infrared spectroscopy) of anionic phospholipid vesicles showed membrane disruption even at low peptide-to-phospholipid ratios, and the effect increases proportionately to the peptide concentration. On the other hand, these biophysical investigations showed that a critical peptide-to-phospholipid ratio around 0.6 is essential for promoting disruption of zwitterionic membranes. In conclusion, this study demonstrates that the binding process of the antimicrobial HSP1-NH2 peptide depends on the membrane composition and peptide concentration.

Publication year: 2021
Authors: I.P.Gomes a, T.L.Santos a, Souza a., L.O.Nunes a, G.A.Cardoso a,b, C.O.Matos c, L.M.F.Costa a, L.M.Lião c, J.M.Resende b, R.M.Verly a

a – Departamento de Química – Universidade Federal dos Vales do Jequitinhonha e Mucuri, 39100-000 Diamantina, MG, Brazil
b – Departamento de Química – Universidade Federal de Minas Gerais, P.O. Box 486, 31270-901 Belo Horizonte, MG, Brazil
c – Instituto de Química – Universidade Federal de Goiás, 74690-900 Goiânia, GO, Brazil

Published in: Biochimica et Biophysica Acta (BBA) - Biomembranes, 2021, Vol. 1863, Issue 1, p. 183449
DOI: 10.1016/j.bbamem.2020.183449


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