α-Tocopherol transfer protein (α-TTP)
α-Tocopherol transfer protein (α-TTP)
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DOI：
10.1016/j.freeradbiomed.2021.09.021
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发表时间：
2021-10-04
影响因子：
7.4
通讯作者：
Kono, Nozomu
中科院分区：
文献类型：
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作者：
Arai, Hiroyuki;Kono, Nozomu
α-生育酚转移蛋白 (α-TTP) 是迄今为止唯一已知的特异性识别α-生育酚 (α-Toc) 的蛋白质，α-生育酚是高等动物中含量最丰富且最具生物活性的维生素 E 形式。 α-TTP 在肝脏中高度表达，其中 α-TTP 在通过血浆脂蛋白吸收的维生素 E 形式中选择 α-Toc，并促进其分泌为循环脂蛋白。因此，α-TTP 是血浆 α-Toc 浓度的主要决定因素。家族性维生素 E 缺乏症，也称为维生素 E 缺乏性共济失调，是由 α-TTP 基因突变引起的。全世界已在α-TTP基因中发现了20多种不同的突变，其中一些错义突变为阐明细胞内α-Toc转运的分子机制提供了有价值的线索。在肝细胞中，α-TTP 通过靶向磷脂酰肌醇磷酸 (PIP)（例如 PI(4,5) P-2）来催化 α-Toc 从内吞区室到质膜 (PM) 的矢量转运。通过在 PM 上结合 PIP，α-TTP 打开覆盖疏水袋的盖子，从而促进结合的 α-Toc 释放到 PM。
alpha-Tocopherol transfer protein (alpha-TTP) is so far the only known protein that specifically recognizes alpha-tocopherol (alpha-Toc), the most abundant and most biologically active form of vitamin E, in higher animals. alpha-TTP is highly expressed in the liver where alpha-TTP selects alpha-Toc among vitamin E forms taken up via plasma lipoproteins and promotes its secretion to circulating lipoproteins. Thus, alpha-TTP is a major determinant of plasma alpha-Toc concentrations. Familial vitamin E deficiency, also called Ataxia with vitamin E deficiency, is caused by mutations in the alpha-TTP gene. More than 20 different mutations have been found in the alpha-TTP gene worldwide, among which some missense mutations provided valuable clues to elucidate the molecular mechanisms underlying intracellular alpha-Toc transport. In hepatocytes, alpha-TTP catalyzes the vectorial transport of alpha-Toc from the endocytotic compartment to the plasma membrane (PM) by targeting phosphatidylinositol phosphates (PIPs) such as PI(4,5) P-2. By binding PIPs at the PM, alpha-TTP opens the lid covering the hydrophobic pocket, thus facilitating the release of bound alpha-Toc to the PM.