The role of N-terminal acetylation of COVID fusion peptides in the interactions with liquid-ordered lipid bilayers.

Autor: Miłogrodzka I; Department of Chemical and Biological Engineering, Monash University, Clayton, VIC, Australia; Australian Synchrotron, 800 Blackburn Road, Clayton, VIC, Australia., Le Brun AP; Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, Australia., Banaszak Holl MM; Department of Chemical and Biological Engineering, Monash University, Clayton, VIC, Australia; Department of Mechanical and Materials Engineering, University of Alabama at Birmingham, Birmingham, AL, USA; Division of Pulmonology, Allergy, and Critical Care Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., van 't Hag L; Department of Chemical and Biological Engineering, Monash University, Clayton, VIC, Australia. Electronic address: leonie.vanthag@monash.edu.
Jazyk: angličtina
Zdroj: Journal of colloid and interface science [J Colloid Interface Sci] 2025 Feb; Vol. 679 (Pt B), pp. 446-456. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1016/j.jcis.2024.10.112
Abstrakt: The partitioning of viral fusion peptides in lipid membranes with varying order was investigated due to the fusion mechanism being a potential therapeutic approach. Using a planar bilayer model and advanced techniques such as neutron reflectometry (NR) and quartz crystal microbalance with dissipation (QCM-D), the structural aspects of peptide-lipid interactions were explored. The study focused on two target membranes: one forming a liquid-ordered domain and the other forming a liquid-disordered domain. Surprisingly, the COVID fusion peptide did not bind significantly to either membrane, as demonstrated by both QCM-D and NR data, suggesting negligible or no interaction with the bilayers. However, the acetylated COVID fusion peptide showed distinct behaviour, indicating a crucial role of N-terminal acetylation in binding to cholesterol-rich liquid-ordered domains. The acetylated peptide induced changes in the structure and thickness of the ordered bilayer with cholesterol whereas proteins and peptides commonly only bind to disordered phases. This study provides valuable insights into the mechanisms of viral membrane fusion and highlights the importance of acetylation in influencing peptide-lipid interactions, laying the groundwork for potential antiviral therapeutic strategies.
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 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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