Protein–Lipid Interactions in Biological Membranes

Abstract

AbstractThe canonical Singer–Nicolson model of lipid bilayers with embedded proteins emphasize the passive barrier properties of the bilayer component. It is, however, becoming increasingly clear that the notion of bilayers as essentially inert two‐dimensional sheets of liquid hydrocarbon is problematic. There is increasing evidence for regulation of integral membrane protein function by the molecular composition of the bilayer matrix. In many cases, the regulation is nonspecific in the sense that the regulation is coupled to a physical property of the bilayer such as equilibrium thickness and spontaneous monolayer curvature. This regulation can be rationalized by considering the hydrophobic matching between proteins and the lipid bilayer. Thus, whenever an integral membane protein undergoes a conformational change involving its hydrophobic transmembrane moiety, part of the free energy associated with the conformational change is determined by the physical properties of the lipid bilayer. This chapter first reviews the basic structural properties of lipid bilayers and the two main structural classes of integral membrane proteins: alpha‐helical bundles and beta‐barrels. Then, examples of recent advances in electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) spectroscopy revealing structural and orientational information about integral membrane protein in fluid lipid bilayers are presented. Finally, a continuum elastic description of protein–lipid interactions is presented with emphasis on how to quantify the energetics of protein–lipid interactions.