ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum
ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum
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DOI：
10.1074/jbc.275.7.4827
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发表时间：
2000-02-18
影响因子：
4.8
通讯作者：
Sitia, R
中科院分区：
文献类型：
--
作者：
Cabibbo, A;Pagani, M;Sitia, R
氧化条件必须保持在内质网（ER），以允许在分泌蛋白质中形成二硫键。在这里，我们报告的哺乳动物基因（ERO 1-L），共享广泛的同源性与酿酒酵母ERO 1基因，在酵母中所需的氧化蛋白折叠的克隆和表征。当在哺乳动物细胞中表达时，人ERO 1-L基因的产物与ER标记物共定位并显示Endo-H-敏感性聚糖。在分离的微粒体中，ERO 1-L表现为II型整合膜蛋白。ERO 1-L能够补充酵母温度敏感突变体ero 1 -1的几个表型性状，包括温度和二硫苏糖醇敏感性，以及羧肽酶Y中的链内二硫键形成，当高度保守的Cys-394或Cys-397中的任一个突变时，ERO 1-L不再具有功能。这些结果强烈表明，ERO 1-L参与哺乳动物细胞中的氧化ER蛋白折叠。
Oxidizing conditions must be maintained in the endoplasmic reticulum (ER) to allow the formation of disulfide bonds in secretory proteins. Here we report the cloning and characterization of a mammalian gene (ERO1-L) that shares extensive homology with the Saccharomyces cerevisiae ERO1 gene, required in yeast for oxidative protein folding. When expressed in mammalian cells, the product of the human ERO1-L gene co localizes with ER markers and displays Endo-H-sensitive glycans, In isolated microsomes, ERO1-L behaves as a type II integral membrane protein. ERO1-L is able to complement several phenotypic traits of the yeast thermosensitive mutant ero1-1, including temperature and dithiothreitol sensitivity, and intrachain disulfide bond formation in carboxypeptidase Y, ERO1-L is no longer functional when either one of the highly conserved Cys-394 or Cys-397 is mutated. These results strongly suggest that ERO1-L is involved in oxidative ER protein folding in mammalian cells.