title: Melittin-Induced Lipid Extraction Modulated by the Methylation Level of Phosphatidylcholine Headgroups.
abstract: Protein- and peptide-induced lipid extraction from membranes is a critical process for many biological events, including reverse cholesterol transport and sperm capacitation. In this work, we examine whether such processes could display specificity for some lipid species. Melittin, the main component of dry bee venom, was used as a model amphipathic α-helical peptide. We specifically determined the modulation of melittin-induced lipid extraction from membranes by the change of the methylation level of phospholipid headgroups. Phosphatidylcholine (PC) bilayers were demethylated either by substitution with phosphatidylethanolamine (PE) or chemically by using mono- and dimethylated PE. It is shown that demethylation reduces the association of melittin with membranes, likely because of the resulting tighter chain packing of the phospholipids, which reduces the capacity of the membranes to accommodate inserted melittin. This reduced binding of the peptide is accompanied by an inhibition of the lipid extraction caused by melittin. We demonstrate that melittin selectively extracts PC from PC/PE membranes. This selectivity is proposed to be a consequence of a PE depletion in the surroundings of bound melittin to minimize disruption of the interphospholipid interactions. The resulting PC-enriched vicinity of melittin would be responsible for the observed formation of PC-enriched lipid/peptide particles resulting from the lipid efflux. These findings reveal that modulating the methylation level of phospholipid headgroups is a simple way to control the specificity of lipid extraction from membranes by peptides/proteins and thereby modulate the lipid composition of the membranes.
authors.affiliation: Department of Chemistry, Center for Self-Assembled Chemical Structures, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Therrien
authors.affiliation: Department of Chemistry, Center for Self-Assembled Chemical Structures, Université de Montréal, Montréal, Québec, Canada. Electronic address: michel.lafleur@umontreal.ca.
authors.forename: Michel
authors.initials: M
authors.lastname: Lafleur
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry*; D008745:Methylation; D010713:Phosphatidylcholines / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D008555:Melitten; C483858:phosphatidylethanolamine