Membrane Composition Modulates Fusion by Altering Membrane Properties and Fusion Peptide Structure

Abstract

Membrane fusion, one of the most essential processes in the life of eukaryotes, occurs when two separate lipid bilayers merge into a continuous bilayer and internal contents of two separated membranes mingle. There is a certain class of proteins that assist the binding of the viral envelope to the target host cell and catalyzing fusion. All class I viral fusion proteins contain a highly conserved 20-25 amino-acid amphipathic peptide at the N-terminus, which is essential for fusion activity and is termed as the 'fusion peptide'. It has been shown that insertion of fusion peptides into the host membrane and the perturbation in the membrane generated thereby is crucial for membrane fusion. Significant efforts have been given in the last couple of decades to understand the lipid-dependence of structure and function of the fusion peptide in membranes to understand the role of lipid compositions in membrane fusion. In addition, the lipid compositions further change the membrane physical properties and alter the mechanism and extent of membrane fusion. Therefore, lipid compositions modulate membrane fusion by changing membrane physical properties and altering structure of the fusion peptide.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Effect of pH on the influenza fusion peptide properties unveiled by constant-pH molecular dynamics simulations combined with experiment

“…The mechanism by which the peptide induces lipid mixing is not fully elucidated, but several recent experimental and computational studies have suggested different modes of action, including altering the membrane curvature, increasing or decreasing lipid order or inducing pore formation and stabilization [14][15][16][17][18][19][20][21][22][23][24][25][26] . A mechanism that has been proposed based on molecular dynamics (MD) simulations asserts that lipid tail protrusion (i.e.…”

Single-cell glycolytic activity regulates membrane tension and HIV-1 fusion

“…HIV fusion, as this line-tension necessary to drive fusion is diminished. Furthermore, sequestration of cholesterol from the host plasma membrane ostensibly increases membrane tension (Fig 8), which has been illustrated previously to collapse hemifusion intermediates [74] in addition to preventing the formation of highly curved intermediates, disfavouring packing defect formation and the generation of nucleation points for two membranes to be joined [73]. Moreover, this increase in membrane tension might in turn have an effect on the optimal hydrophobic equilibrium between ordered and disordered lipid domains needed to complete the fusion reaction [21,29].…”

“…Moreover, the line tension created at lipid domain boundaries drives gp41-mediated fusion, owing to the mismatches in lipid length occurring at Lo and Ld boundaries, most likely creating membrane curvature which favours virion fusion [21] (Fig 8). Cholesterol and other ordered lipids are known to maintain negative spontaneous curved membrane domains, which facilitates the creation of a fusion stalk by reducing its formation energy in addition to enabling its progression to fusion pore formation [73]. The sequestration of cholesterol from the host membrane in glycolytically-inactivated cells arrests…”

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