Gong E L, Tan C S, Shoukry M I, Rubin E M, Nichols A V
Life Sciences Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Biochim Biophys Acta. 1994 Aug 4;1213(3):335-42. doi: 10.1016/0005-2760(94)00062-x.
Mouse and human plasma apolipoprotein A-I (apo A-Im and apo A-Ih, respectively) were investigated to compare their molecular properties in solution, their incorporation into palmitoyloleoylphosphatidylcholine-apo A-I (POPC-apo A-I) discoidal complexes; their structural stability in discoidal complexes and high-density lipoproteins (HDL), and their effect on structural rearrangement of discoidal complexes upon interaction with low-density lipoproteins (LDL). Unlike apo A-Ih, only minimal concentration-dependent self-association was observed for apo A-Im. While both apo A-Im and apo A-Ih formed discoidal complexes of distinct composition and size that reflected reassembly molar ratios of POPC/apo A-I, apo A-Im demonstrated specific deficiencies in formation of larger-sized complexes. Denaturation of both apo A-Im- or apo A-Ih-containing complexes and HDL with guanidine hydrochloride (GuHCl) indicated significantly reduced stabilization of apo A-Im by lipid in these particles. Interaction of apo A-Im- or apo A-Ih-containing discoidal complexes with human plasma LDL revealed a more extensive conversion of apo A-Im-complexes to smaller species. Mean hydrophobicities and mean hydrophobic moments of amphipathic helical segments in apo A-Im and apo A-Ih were compared; differences potentially contributing to differential lipid-binding properties between apo A-Im and apo A-Ih were identified. Our results demonstrate differences between apo A-Im and apo A-Ih that may contribute to the major changes in plasma HDL distribution and function observed in apo A-Ih transgenic mice.
对小鼠和人血浆载脂蛋白A-I（分别为载脂蛋白A-Im和载脂蛋白A-Ih）进行了研究，以比较它们在溶液中的分子特性、它们掺入棕榈油酰油酰磷脂酰胆碱-载脂蛋白A-I（POPC-载脂蛋白A-I）盘状复合物中的情况；它们在盘状复合物和高密度脂蛋白（HDL）中的结构稳定性，以及它们与低密度脂蛋白（LDL）相互作用时对盘状复合物结构重排的影响。与载脂蛋白A-Ih不同，仅观察到载脂蛋白A-Im有最小的浓度依赖性自缔合。虽然载脂蛋白A-Im和载脂蛋白A-Ih都形成了组成和大小不同的盘状复合物，这反映了POPC/载脂蛋白A-I的重组摩尔比，但载脂蛋白A-Im在形成较大尺寸复合物方面表现出特定缺陷。用盐酸胍（GuHCl）使含载脂蛋白A-Im或载脂蛋白A-Ih的复合物以及HDL变性，表明这些颗粒中的脂质对载脂蛋白A-Im的稳定作用显著降低。含载脂蛋白A-Im或载脂蛋白A-Ih的盘状复合物与人血浆LDL相互作用，显示载脂蛋白A-Im复合物向较小物种的转化更为广泛。比较了载脂蛋白A-Im和载脂蛋白A-Ih中两亲性螺旋段的平均疏水性和平均疏水矩；确定了可能导致载脂蛋白A-Im和载脂蛋白A-Ih之间脂质结合特性差异的差异。我们的结果证明了载脂蛋白A-Im和载脂蛋白A-Ih之间的差异，这可能导致在载脂蛋白A-Ih转基因小鼠中观察到的血浆HDL分布和功能的主要变化。
