A Fusion Peptide's Interactions with Cholesterol in a Lipid Bilayer Membrane

Fusion peptides (FPs) are short sequences within larger viral proteins that play a major role in the infection of a cell. Isolated FPs can also interact directly with the cellular membrane and cause fusion. The 23 amino acid residue peptide from the HIV-1 virus gp41 coat glycoprotein is one such FP. Here, a study of the interaction of a less fusogenic form of the HIV-1 FP with lipid bilayer membranes containing different amounts of cholesterol (Chol) is presented. Chol strongly influences the interaction of the peptide with the lipid bilayer in a concentration-dependent manner. When sufficient Chol is present, fusion can take place. Small-angle neutron scattering and circular dichroism spectroscopy experiments were complemented with molecular dynamics simulations of the systems studied to gain additional insight into how Chol influences the behavior. The results reveal surprising new information about lipid-specific interactions that the peptide has in the bilayer.