Nagao Kohjiro, Kimura Yasuhisa, Ueda Kazumitsu
Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8502, Japan.
Biochim Biophys Acta. 2012 Mar;1821(3):530-5. doi: 10.1016/j.bbalip.2011.06.024. Epub 2011 Jul 1.
ATP-binding cassette protein A1 (ABCA1) plays a pivotal role in cholesterol homeostasis by generating high-density lipoprotein (HDL). Apolipoprotein A-I (apoA-I), a lipid acceptor for ABCA1, reportedly interacts with ABCA1. However, it has also been proposed that apoA-I interacts with ABCA1-generated special domains on the plasma membrane, but apart from ABCA1, and solubilizes membrane lipids. To determine the importance of the apoA-I-ABCA1 interaction in HDL formation, the electrostatic interaction between apoA-I and ABCA1, which mediates the interaction between apoB100 in low-density lipoprotein particles (LDL) and LDL receptor, was analyzed. The apoA-I binding to ABCA1 and the cross-linking between them were inhibited by the highly charged molecules heparin and poly-L-lysine. Treating cells with membrane impermeable reagents that specifically react with primary amino groups abolished the interaction between apoA-I and ABCA1. However, these reagents did not affect the characteristic tight ATP binding to ABCA1. These results suggest that lysine residues in the extracellular domains of ABCA1 contribute to the interaction with apoA-I. The electrostatic interaction between ABCA1 and apoA-I is predicted to be the first step in HDL formation. This article is part of a Special Issue entitled Advances in high density lipoprotein formation and metabolism: a tribute to John F. Oram (1945-2010).
ATP结合盒转运蛋白A1（ABCA1）通过生成高密度脂蛋白（HDL）在胆固醇稳态中发挥关键作用。据报道，载脂蛋白A-I（apoA-I）作为ABCA1的脂质受体，可与ABCA1相互作用。然而，也有人提出apoA-I与ABCA1在质膜上生成的特殊结构域相互作用，但该结构域独立于ABCA1，可溶解膜脂。为了确定apoA-I与ABCA1相互作用在HDL形成中的重要性，分析了介导低密度脂蛋白颗粒（LDL）中的载脂蛋白B100与LDL受体相互作用的apoA-I与ABCA1之间的静电相互作用。带高电荷的分子肝素和聚-L-赖氨酸可抑制apoA-I与ABCA1的结合及其交联。用与伯氨基特异性反应的膜不透性试剂处理细胞可消除apoA-I与ABCA1之间的相互作用。然而，这些试剂并不影响ABCA1与ATP的特异性紧密结合。这些结果表明，ABCA1胞外结构域中的赖氨酸残基有助于与apoA-I的相互作用。ABCA1与apoA-I之间 的静电相互作用预计是HDL形成的第一步。本文是名为“高密度脂蛋白形成与代谢进展：纪念约翰·F·奥勒姆（1945 - 2010）”特刊的一部分。
