アポリポタンパク-脂質膜相互作用によるディスク状複合体形成と高密度リポタンパク質(HDL)形成原理の考察(誌上シンポジウム)  [in Japanese] Disk-like Complex Formation by Apolipoprotein-Lipid Membrane Interaction and Relevance to High-Density Lipoprotein Formation(Symposium Reviews)  [in Japanese]

The interaction of apolipoprotein A-I (apoA-I) with transmembrane ATP-binding cassette transporter A1 (ABCA1) is a crucial step for high-density lipoprotein (HDL) formation, however, its molecular mechanism is less well understood. Here, we used apoA-I and its model peptide, Ac-18A-NH_2, to investigate their interaction with mixed membranes of phosphatidylcholine (PC) with phosphatidylethanolamine (PE) or sphingomyelin (SM). It was shown that PE, possessing the negative spontaneous curvature, increased both the degree of hydration at the membrane interface and the acyl chain order, and that Ac-18A-NH_2 had opposite effects to PE, since the α-helix formation at the membrane surface induced positive curvature strain. In addition, increased PE in PC/PE large unilamellar vesicles (LUVs) enhanced the peptide's binding. Although SM significantly lowered the peptide binding capacity, the peptide's binding to PC/SM LUV led to membrane disruption. The interaction with PC/SM LUVs was then investigated using ApoA-I. The spontaneous rHDL formation from pure PC LUV proceeded very slowly at 37℃, but SM-rich PC/SM LUVs, which are in a gel/liquid-disordered (L_d) phase at this temperature, were rapidly solubilized to form rHDL by apoA-I. The addition of cholesterol decreased the rate of the rHDL formation and induced the selective extraction of lipids by apoA-I, which preferably extracted lipids of L_d phase rather than lipids of liquid-ordered (L_o) phase. These results suggest that heterogeneous interface of the mixed membranes facilitates the insertion of apoA-I and induces L_d phase-selective lipid extraction to form rHDL, and are compatible with recent cell works on the apoA-I-dependent HDL generation.