Abstract
The membrane disruption activities of kalata B1 (kB1) were investigated using molecular dynamics simulations with membrane models. The models were constructed to mimic the lipid microdomain formation in membranes of HIV particle, HIV-infected cell, and host cell. The differences in the lipid ratios of these membranes caused the formation of liquid ordered (lo) domains of different sizes, which affected the binding and activity of kB1. Stronger kB1 disruptive activity was observed for the membrane with small sized lo domain. Our results show that kB1 causes membrane leaking without bilayer penetration. The membrane poration mechanism involved in the disorganization of the lo domain and in cholesterol inter-leaflet translocation is described. This study enhances our understanding of the membrane activity of kB1, which may be useful for designing novel and potentially therapeutic peptides based on the kB1 framework.
Highlights
Molecular dynamics exploration of poration and leaking caused by Kalata B1 in HIV-infected cell membrane compared to host and HIV membranes
In the inner layer, the amplitude was approximately 0.82 nm higher. These findings indicate that the surface area of the membrane, which was inversely correlated to size of the lo domain, regulated the number of kalata B1 (kB1) molecules that bound to the membrane
We investigated several aspects of the interplay between the amounts of lipids in the VI, IN and HO membranes and the membrane disruption activity of kB1
Summary
Molecular dynamics exploration of poration and leaking caused by Kalata B1 in HIV-infected cell membrane compared to host and HIV membranes. The differences in the lipid ratios of these membranes caused the formation of liquid ordered (lo) domains of different sizes, which affected the binding and activity of kB1. The bioactivities of the cyclic peptide arise via a common mechanism that is related to its ability to bind and disrupt the cell membrane[8]. The mechanism is initiated by the absorption of kB1 molecules onto the membrane surface[9, 10] As it is energetically unfavorable for kB1 to penetrate the membrane[11], kB1 prefers the area referred to as the membrane interfacial zone[10, 11], which includes atoms at the membrane-water interface and the atoms of lipid hydrocarbon chains[12]. Phospholipids with phosphatidylethanolamine (PE) polar groups have been reported to promote an interaction between kB1 and the membrane and to enhance the disrupting activity of the peptide[14, 16,17,18,19]
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