Biochemical characterization of the human copper transporter Ctr1
Biochemical characterization of the human copper transporter Ctr1
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DOI：
10.1074/jbc.m104728200
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发表时间：
2002-02-08
影响因子：
4.8
通讯作者：
Thiele, DJ
中科院分区：
文献类型：
--
作者：
Lee, J;Peña, MMO;Thiele, DJ
微量金属铜是许多生物过程的重要辅因子，包括线粒体氧化磷酸化、自由基解毒、神经递质合成和成熟以及铁代谢。因此，铜在细胞表面的转运和铜向细胞内蛋白质的递送是正常生理学中的关键事件。对哺乳动物质膜铜吸收的分子和生化机制知之甚少。在这里，我们证明，人类Ctr 1（hCtr 1）是一个组成部分的铜转运机械在质膜。hCtr 1以时间依赖性和可饱和的方式以高亲和力转运铜，并且是金属特异性的。hCtr 1介导的Cu-64转运是一个不依赖能量的过程，并受到细胞外酸性pH和高K+浓度的刺激。hCtr 1在哺乳动物细胞中以同源多聚体的形式存在于质膜上。这是人类铜转运蛋白hCtr 1的生化特性的第一份报告，这是重要的了解哺乳动物的铜转运在质膜的机制。
The trace metal copper is an essential cofactor for a number of biological processes including mitochondrial oxidative phosphorylation, free radical detoxification, neurotransmitter synthesis and maturation, and iron metabolism. Consequently, copper transport at the cell surface and the delivery of copper to intracellular proteins are critical events in normal physiology. Little is known about the molecules and biochemical mechanisms responsible for copper uptake at the plasma membrane in mammals. Here, we demonstrate that human Ctr1 (hCtr1) is a component of the copper transport machinery at the plasma membrane. hCtr1 transports copper with high affinity in a time-dependent and saturable manner and is metal-specific. hCtr1-mediated Cu-64 transport is an energy-independent process and is stimulated by extracellular acidic pH and high K+ concentrations. hCtr1 exists as a homomultimer at the plasma membrane in mammalian cells. This is the first report on the biochemical characterization of the human copper transporter hCtr1, which is important for understanding mechanisms for mammalian copper transport at the plasma membrane.