AtERO1 and AtERO2 Exhibit Differences in Catalyzing Oxidative Protein Folding in the Endoplasmic Reticulum
AtERO1 and AtERO2 Exhibit Differences in Catalyzing Oxidative Protein Folding in the Endoplasmic Reticulum
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AtERO1 和 AtERO2 在催化内质网氧化蛋白折叠方面表现出差异
DOI：
10.1104/pp.19.00020
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发表时间：
2019-08-01
期刊：
影响因子：
7.4
通讯作者：
Lu, Dongping
中科院分区：
文献类型：
--
作者：
Fan, Fenggui;Zhang, Yini;Lu, Dongping
二硫键对于内质网（ER）中真核分泌蛋白和膜蛋白的折叠是必不可少的，并且ER氧化还原蛋白-1（Ero 1）及其同源物是在ER中提供氧化等价物的主要二硫键供体。虽然Ero 1在酵母（酿酒酵母）和哺乳动物中的同源物已被广泛研究，但植物Ero 1功能的机制远未被理解。在这里，我们发现，拟南芥（拟南芥）ERO 1和它的同系物AtERO 2所需的ER中的氧化蛋白质折叠。AtERO 1的功能需要外部活性位点、内部活性位点和长程非催化二硫键。有趣的是，AtERO 1和AtERO 2也表现出显着差异。ero 1植物比ero 2植物对还原胁迫更敏感。在体内，AtERO 1和AtERO 2都有两种不同的氧化亚型（Ox 1和Ox 2），这是由推定的调节二硫化物的形成或断裂决定的。AtERO 1主要以Ox 1氧化还原态存在，而更多的AtERO 2以Ox 2态存在。此外，AtERO 1在体外表现出比AtERO 2更强的氧化蛋白折叠活性。两者合计，AtERO 1和AtERO 2都需要调节ER中有效和忠实的氧化蛋白质折叠，但AtERO 1可能作为相对于AtERO 2的主要巯基氧化酶。
Disulfide bonds are essential for the folding of the eukaryotic secretory and membrane proteins in the endoplasmic reticulum (ER), and ER oxidoreductin-1 (Ero1) and its homologs are the major disulfide donors that supply oxidizing equivalents in the ER. Although Ero1 homologs in yeast (Saccharomyces cerevisiae) and mammals have been extensively studied, the mechanisms of plant Ero1 functions are far less understood. Here, we found that both Arabidopsis (Arabidopsis thaliana) ERO1 and its homolog AtERO2 are required for oxidative protein folding in the ER. The outer active site, the inner active site, and a long-range noncatalytic disulfide bond are required for AtERO1's function. Interestingly, AtERO1 and AtERO2 also exhibit significant differences. The ero1 plants are more sensitive to reductive stress than the ero2 plants. In vivo, both AtERO1 and AtERO2 have two distinct oxidized isoforms (Ox1 and Ox2), which are determined by the formation or breakage of the putative regulatory disulfide. AtERO1 is mainly present in the Ox1 redox state, while more AtERO2 exists in the Ox2 state. Furthermore, AtERO1 showed much stronger oxidative protein-folding activity than AtERO2 in vitro. Taken together, both AtERO1 and AtERO2 are required to regulate efficient and faithful oxidative protein folding in the ER, but AtERO1 may serves as the primary sulfhydryl oxidase relative to AtERO2.