Peptide Lipidation by Acyl Transfer from Membrane Lipids and Lyso-Lipids

Acyl group transfer to membrane-active peptides (exemplified by melittin, magainin II, PGLa and penetratin) occurs following their addition to phospholipid membranes composed of phospholipids (doi: 10.1016/j.jmb.2013.07.013). This chemical reactivity, termed intrinsic lipidation, exhibits modest selectivity according to the lipid composition of the membrane. Transfer is favored in mixtures of PC with PS and PG. Mixtures of PC with PE exhibit more complex patterns of reactivity. Lyso-PCs are also able to act as acyl group donors. The intrinsic lipidation of melittin occurs below the threshold peptide to lipid ratio for toroidal pore formation and over physiologically significant ranges of temperature (20-37 °C) and ionic strength (0-150 mM NaCl). Intrinsic lipidation is able to generate significant chemical complexity from a small number of components. As lipidation induces significant changes to the structure and membrane affinity of peptides, this process has significant implications for any procedure that involves peptide addition to lipid membranes. In addition to accounting for behavior such as irreversible binding in peptide-lipid binding experiments, intrinsic lipidation provides an explanation for a number of unusual lipidation patterns found in membrane proteins.View Large Image | View Hi-Res Image | Download PowerPoint Slide