gp41 Fusion Peptide Alters the Properties of Lipid Monolayer at the Air-Water Interface in a Cholesterol-Dependent Fashion: Implications in Membrane Fusion.

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Tác giả: Hirak Chakraborty, Sajal K Ghosh, Manbit Subhadarsi Panda, Sonam Raghav

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : Langmuir : the ACS journal of surfaces and colloids , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 741858

Enveloped viruses fuse at the cell surface or the endosome after the virus is endocytosed for cellular entry. Membrane fusion is a crucial stage in infection regardless of the pathway. The effect of the fusion peptide, a 20-25 N-terminal residue of the fusion domain, facilitates membrane fusion in multiple ways. In this work, we have assessed the effect of the gp41 fusion peptide from the human immunodeficiency virus (HIV) on the DOPC/DOPE/DOPG monolayers with varying concentrations of cholesterol. The ability of the gp41 fusion peptide to promote fusion among small unilamellar vesicles (SUVs) was examined with the same lipid composition, for which we measured the monolayer properties. Our results show that the peptide is adsorbed on the lipid headgroup in the aqueous subphase in the absence of cholesterol, whereas it gets integrated (orients parallel to the lipid molecule) with the addition of cholesterol in the lipid mixture. To support our findings from monolayer measurements, we have further assessed the peptide's impact on the depth-dependent ordering and polarity of the bilayer membrane using steady-state and time-resolved fluorescence techniques. The peptide-induced change in the elastic compressional modulus also depends on the mole fraction of cholesterol in the lipid mixture. We further compared the ability of the peptide to induce fusion with the change in monolayer properties. Our results demonstrate that the orientation of the peptide in the lipid is crucial for its fusogenic ability as the percentage change in the lipid mixing is correlated to the change in area lift-off parameter in monolayer measurements. Taken together, our results offer a better understanding of the cholesterol-dependent fusogenic ability of the gp41 fusion peptide.
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