Secondary structure propensities of the Ebola delta peptide E40 in solution and model membrane environments.

Autor: Li J; School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Australia., Eagles DA; Institute of Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Tucker IJ; Institute of Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Pereira Schmidt AC; School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Australia., Deplazes E; School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Australia. Electronic address: e.deplazes@uq.edu.au.
Jazyk: angličtina
Zdroj: Biophysical chemistry [Biophys Chem] 2024 Nov; Vol. 314, pp. 107318. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1016/j.bpc.2024.107318
Abstrakt: The Ebola delta peptide is an amphipathic, 40-residue peptide encoded by the Ebola virus, referred to as E40. The membrane-permeabilising activity of the E40 delta peptide has been demonstrated in cells and lipid vesicles suggesting the E40 delta peptide likely acts as a viroporin. The lytic activity of the peptide increases in the presence of anionic lipids and a disulphide bond in the C-terminal part of the peptide. Previous in silico work predicts the peptide to show a partially helical structure, but there is no experimental information on the structure of E40. Here, we use circular dichroism spectroscopy to report the secondary structure propensities of the reduced and oxidised forms of the E40 peptide in water, detergent micelles, and lipid vesicles composed of neutral and anionic lipids (POPC and POPG, respectively). Results indicate that the peptide is predominately a random coil in solution, and the disulphide bond has a small but measurable effect on peptide conformation. Secondary structure analysis shows large uncertainties and dependence on the reference data set and, in our system, cannot be used to accurately determine the secondary structure motifs of the peptide in membrane environments. Nevertheless, the spectra can be used to assess the relative changes in secondary structure propensities of the peptide depending on the solvent environment and disulphide bond. In POPC-POPG vesicles, the peptide transitions from a random coil towards a more structured conformation, which is even more pronounced in negatively charged SDS micelles. In vesicles, the effect depends on the peptide-lipid ratio, likely resulting from vesicle surface saturation. Further experiments with zwitterionic POPC vesicles and DPC micelles show that both curvature and negatively charged lipids can induce a change in conformation, with the two effects being cumulative. Electrostatic screening from Na + ions reduced this effect. The oxidised form of the peptide shows a slightly lower propensity for secondary structure and retains a more random coil conformation even in the presence of PG-PC vesicles.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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