Pollard M G, Travers K J, Weissman J S
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0450, USA.
Mol Cell. 1998 Jan;1(2):171-82. doi: 10.1016/s1097-2765(00)80018-0.
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.
许多进入分泌途径的蛋白质的结构依赖于二硫键的稳定作用。为了支持二硫键连接的折叠过程，与胞质溶胶的高度还原环境相比，内质网（ER）必须维持一个强氧化环境。我们在此报告一种新型的内质网驻留蛋白Ero1p的鉴定和特性。Ero1p中的突变会导致对还原剂二硫苏糖醇（DTT）极度敏感，而过表达则赋予DTT抗性。令人惊讶的是，Ero1p功能受损会导致二硫键稳定的蛋白质以还原的、非天然的形式在内质网中滞留，而不影响无二硫键蛋白质的结构成熟。我们得出结论，内质网中存在二硫键连接的蛋白质折叠所需的特定细胞氧化还原机制，且Ero1p是该机制的一个重要组成部分。
