Steroidogenic acute regulatory protein (StAR) is a sterol transfer protein
Steroidogenic acute regulatory protein (StAR) is a sterol transfer protein
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DOI：
10.1074/jbc.273.41.26285
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发表时间：
1998-10-09
影响因子：
4.8
通讯作者：
Strauss, JF
中科院分区：
文献类型：
--
作者：
Kallen, CB;Billheimer, JT;Strauss, JF
类固醇生成急性调节蛋白（StAR）通过增强底物胆固醇从线粒体外膜到内膜上的胆固醇侧链裂解酶系统的递送，在类固醇生成中发挥关键作用。缺乏第一个 N 端 62 个氨基酸残基（包括线粒体靶向序列）的重组 StAR 蛋白被证明可以以剂量、时间和温度依赖性方式刺激胆固醇和 β-谷甾醇从脂质体转移到热处理的线粒体。不能通过分离的线粒体刺激类固醇生成的重组突变StAR蛋白不能促进甾醇转移。与更混杂的脂质转移蛋白甾醇载体蛋白 2 (SCP2) 不同，StAR 在我们的检测系统中不会刺激磷脂酰胆碱转移。重组StAR蛋白增加了胆固醇向热处理的微粒体以及经热处理和胰蛋白酶处理的线粒体的转移。这些观察结果表明，StAR 具有甾醇转移活性，这可能反映了增强胆固醇从富含甾醇的供体膜上解吸的能力。我们认为，StAR 促进甾醇转移的能力解释了其类固醇生成活性。
Steroidogenic acute regulatory protein (StAR) plays a critical role in steroidogenesis by enhancing the delivery of substrate cholesterol from the outer mitochondrial membrane to the cholesterol side chain cleavage enzyme system on the inner membrane. A recombinant StAR protein lacking the first N-terminal 62 amino acid residues that includes the mitochondrial targeting sequence was shown to stimulate the transfer of cholesterol and beta-sitosterol from liposomes to heat-treated mitochondria in a dose-, time-, and temperature-dependent manner. A recombinant mutant StAR protein that cannot stimulate steroidogenesis by isolated mitochondria did not promote sterol transfer. Unlike the more promiscuous lipid transfer protein, sterol carrier protein 2 (SCP2), StAR did not stimulate phosphatidylcholine transfer in our assay system. The recombinant StAR protein increased cholesterol transfer to heat-treated microsomes as well as to heat- and trypsin-treated mitochondria. These observations demonstrate that StAR has sterol transfer activity, which may reflect an ability to enhance desorption of cholesterol from sterol-rich donor membranes. We suggest that the ability of StAR to promote sterol transfer explains its steroidogenic activity.