Ero1p: A novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum
Ero1p: A novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum
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DOI：
10.1016/s1097-2765(00)80018-0
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发表时间：
1998-01-01
期刊：
影响因子：
16
通讯作者：
Weissman, JS
中科院分区：
文献类型：
--
作者：
Pollard, MG;Travers, KJ;Weissman, JS
进入分泌途径的许多蛋白质的结构依赖于二硫键的稳定。为了支持二硫键连接的折叠，内质网（ER）必须保持一个强氧化环境相比，高度还原的环境的胞质溶胶。我们在这里报告的Ero 1 p，一种新的和必需的ER-居民蛋白的鉴定和表征。Ero 1 p的突变导致对还原剂DTT的极端敏感性，而过表达赋予DTT抗性。引人注目的是，Ero 1 p功能受损导致二硫键稳定蛋白质以还原的非天然形式保留在ER中，同时不影响无二硫键蛋白质的结构成熟。我们的结论是，存在一个特定的细胞氧化还原机制所需的二硫键连接的蛋白质折叠在ER和Ero 1 p是这个机器的重要组成部分。
The structure of many proteins entering the secretory pathway is dependent on stabilization by disulfide bonds. To support disulfide-linked folding, the endoplasmic reticulum (ER) must maintain a strongly oxidizing environment compared to the highly reduced environment of the cytosol. We report here the identification and characterization of Ero1p, a novel and essential ER-resident protein. Mutations in Ero1p cause extreme sensitivity to the reducing agent DTT, whereas overexpression confers DTT resistance. Strikingly, compromised Ero1p function results in ER retention of disulfide-stabilized proteins in a reduced, nonnative form, while not affecting structural maturation of a disulfide-free protein. We conclude that there exists a specific cellular redox machinery required for disulfide-linked protein folding in the ER and that Ero1p is an essential component of this machinery.