The roles of the diversity of amphipathic lipids in shaping membranes by membrane-shaping proteins

Abstract

Lipid compositions of cells differ according to cell types and intracellular organelles. Phospholipids are major cell membrane lipids and have hydrophilic head groups and hydrophobic fatty acid tails. The cellular lipid membrane without any protein adapts to spherical shapes, and protein binding to the membrane is thought to be required for shaping the membrane for various cellular events. Until recently, modulation of cellular lipid membranes was initially shown to be mediated by proteins recognizing lipid head groups, including the negatively charged ones of phosphatidylserine and phosphoinositides. Recent studies have shown that the abilities of membrane-deforming proteins are also regulated by the composition of fatty acid tails, which cause different degrees of packing defects. The binding of proteins to cellular lipid membranes is affected by the packing defects, presumably through modulation of their interactions with hydrophobic amino acid residues. Therefore, lipid composition can be characterized by both packing defects and charge density. The lipid composition regarding fatty acid tails affects membrane bending via the proteins with amphipathic helices, including those with the ArfGAP1 lipid packing sensor (ALPS) motif and via membrane-deforming proteins with structural folding, including those with the Bin–Amphiphysin–Rvs167 (BAR) domains. This review focuses on how the fatty acid tails, in combination with the head groups of phospholipids, affect protein-mediated membrane deformation.