Planar aggregation of the influenza viral fusion peptide alters membrane structure and promotes poration
Year: 2024
Type: conference-paper
Abstract: Formation of antiparallel FP dimers is highly favorable, driven primarily by peptide-peptide contacts, and not strongly influenced by membrane composition • Higher order clustering of FP is membrane dependent: • Cholesterol presence favors large aggregates with little lipid separating dimers • In POPC, interfaces separated by a single lipid layer are also favorable • In all systems, POPC is enriched around FP • Lipid composition under peptide aggregates is influenced by spontaneous curvature generation of lipids: • Lipids that generate negative spontaneous curvature are enriched • OPC (generates positive spontaneous curvature) is depleted • Enrichment of chol or DOG under FP may generate negative curvature, stabilizing tetramer formation • Hypothesize that a single layer of lipids between adjacent peptides destabilizes the bilayer, facilitating poration -potentially explaining why cholesterol inhibits poration This work was supported by the Intramural Program of the National Heart Lung and Blood Institute of the National Institutes of Health, Bethesda MD, USA, and utilized high performance computational resources at the National Institutes of Health (NHLBI LoBoS and HPC Biowulf clusters) and Anton 2 (PSC).Simulation snapshots rendered using VMD [9] .Previous experiments and simulations have shown the ability of the isolated FP domain to aggregate when membrane-bound, and form pores in model membrane systems [2,3] ; poration was demonstrated to be inhibited by cholesterol.It was hypothesized that FP clustering promotes poration by decreasing the hydrophobic thickness a pore must span in order to form.
Source: European Peptide Symposium (EPS)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4403190687