Position 834 in TM6 plays an important role in cholesterol and phosphatidylcholine transport by ABCA1
Position 834 in TM6 plays an important role in cholesterol and phosphatidylcholine transport by ABCA1
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TM6 中的 834 位在 ABCA1 转运胆固醇和磷脂酰胆碱中发挥重要作用
DOI：
10.1080/09168451.2014.993358
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Kazumitsu Ueda
中科院分区：
文献类型：
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作者：
Shimpei Ito;Kohjiro Nagao;Yasuhisa Kimura;Michinori Matsuo;Noriyuki Kioka;Kazumitsu Ueda
三磷酸腺苷结合盒蛋白A1(ABCA1)通过产生新生高密度脂蛋白(HDL)，在清除外周细胞中多余的胆固醇方面起着关键作用。然而，目前尚不清楚是否磷脂和胆固醇都通过ABCA1直接负载到载脂蛋白A-I(apoA-I)上。为了确定ABCA1中参与底物识别和转运的氨基酸残基，我们对人ABCA1的L821-E843残基进行了精氨酸扫描突变，并预测了每个残基所处的环境。每个突变体的相对表面表达表明，L821-E843残基以TM6的形式穿过质膜，TM6的四个残基(S826、F830、L834和V837)暴露在ABCA1的亲水性内腔中。此外，我们还证明了L834对ABCA1的功能至关重要。
ATP-binding cassette protein A1 (ABCA1) plays a key role in eliminating excess cholesterol from peripheral cells by generating nascent high-density lipoprotein (HDL). However, it remains unclear whether both phospholipids and cholesterol are directly loaded onto apolipoprotein A-I (apoA-I) by ABCA1. To identify the amino acid residues of ABCA1 involved in substrate recognition and transport, we applied arginine scan mutagenesis to residues L821–E843 of human ABCA1 and predicted the environment to which each residue is exposed. The relative surface expression of each mutant suggested that residues L821–E843 pass through the plasma membrane as TM6, and the four residues (S826, F830, L834, and V837) of TM6 are exposed to the hydrophilic internal cavity of ABCA1. Furthermore, we showed that L834 is critical for the function of ABCA1.