Effects of membrane structure on apolipoprotein A-I binding to lipid

Abstract

Interaction of apolipoproteins with lipid surfaces plays crucial roles in lipoprotein metabolism and cholesterol homeostasis. In this study, to understand the detailed mechanism by which apolipoprotein (apo) A-I associates with plasma membrane and lipoprotein particles, we investigated the effects of lipid composition and surface curvature on the lipid-apoA-I interactions. ApoA-I binding to lipid particles depends on membrane structure. Fluorescence and 13C-NMR measurements revealed that apoA-I recognizes headgroup separation (hydrated space) between phospholipid molecules and displaces water molecules from the surface when it binds. At the surface monolayers of lipoprotein particles, interpenetration of core triglyceride molecules with phospholipid molecules appears to occur to alter the surface structure. ApoA-I binding to lipid membrane induces an increase in α-helical structure. This α-helix formation generates exothermic heat and promotes apoA-I binding to lipid. However, binding of apoA-I to small emulsions exhibited endothermic heat although apoA-I increases α-helical content. Taken together, these observations suggest that the presence of core triglyceride modifies the highly curved emulsion surface and thereby the thermodynamics of apoA-I binding in a manner that compensates for the exothermic heat generated by α-helix formation. © 2007 The Pharmaceutical Society of Japan.