Interaction of Two Amphipathic α-Helix Bundle Proteins, ApoLp-III and ApoE 3, with the Oil–Aqueous Interface
Interaction of Two Amphipathic α-Helix Bundle Proteins, ApoLp-III and ApoE 3, with the Oil–Aqueous Interface
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两种两亲性 α-螺旋束蛋白 ApoLp-III 和 ApoE 3 与油水界面的相互作用
DOI：
10.1021/acs.jpcb.1c00271
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Kooijman, Edgar E.
中科院分区：
文献类型：
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作者：
Mirheydari, Mona;Putta, Priya;Mann, Elizabeth K.;Kooijman, Edgar E.
蛋白质与脂类的相互作用支配着脂蛋白颗粒的结构和功能，脂蛋白颗粒通过血流运输中性脂类和其他疏水性物质。载脂蛋白覆盖在脂蛋白颗粒的表面，包括低密度脂蛋白(LDL)和高密度脂蛋白(HDL)，并决定其功能。以前的工作主要集中在从这些载脂蛋白中提取的小肽，或者使用诸如朗缪尔单分子层或脂盘实验等人工脂系统来确定载脂蛋白如何与中性脂界面相互作用。在这里，我们集中在许多中性脂结合蛋白中发现的一个反复出现的蛋白质结构域，即两亲性α-螺旋束。我们使用液滴张力计来研究油滴上的蛋白质-脂质相互作用，它模拟了真实的脂蛋白界面。ApoE3的N端和全长apoLp-III作为模型蛋白。我们发现，每种蛋白质都以独特的方式与油-水界面的脂单分子层相互作用。我们第一次证明了螺旋束的展开对于蛋白质正确插入油水界面的脂单分子层是至关重要的，并且特定的膜脂在液滴大小波动时促进了蛋白质的重新结合。这些结果为两亲性载脂蛋白α-螺旋束如何与中性脂质颗粒相互作用提供了新的线索。
Protein–lipid interactions govern the structure and function of lipoprotein particles, which transport neutral lipids and other hydrophobic cargo through the blood stream. Apolipoproteins cover the surface of lipoprotein particles, including low-density (LDL) and high-density (HDL) lipoproteins, and determine their function. Previous work has focused on small peptides derived from these apolipoproteins or used such artificial lipid systems as Langmuir monolayers or the lipid disc assay to determine how apolipoproteins interact with the neutral lipid interface. Here, we focus on a recurring protein domain found in many neutral lipid-binding proteins, the amphipathic α-helix bundle. We use liquid droplet tensiometry to investigate protein–lipid interactions on an oil droplet, which mimics the real lipoprotein interface. The N-terminus of apoE 3 and full-length apoLp-III serve as model proteins. We find that each protein interacts with lipid monolayers at the oil–aqueous interface in unique ways. For the first time, we show that helix bundle unfolding is critical for proper protein insertion into the lipid monolayer at the oil–aqueous interface and that specific membrane lipids promote the rebinding of protein upon fluctuation in droplet size. These results shed new light on how amphipathic apolipoprotein α-helix bundles interact with neutral lipid particles.