National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Biochem J. 2011 Feb 15;434(1):113-21. doi: 10.1042/BJ20101357.
In eukaryotes, disulfide bonds are formed in the endoplasmic reticulum, facilitated by the Ero1 (endoplasmic reticulum oxidoreductin 1) oxidase/PDI (protein disulfide-isomerase) system. Mammals have two ERO1 genes, encoding Ero1α and Ero1β proteins. Ero1β is constitutively expressed in professional secretory tissues and induced during the unfolded protein response. In the present work, we show that recombinant human Ero1β is twice as active as Ero1α in enzymatic assays. Ero1β oxidizes PDI more efficiently than other PDI family members and drives oxidative protein folding preferentially via the active site in the á domain of PDI. Our results reveal that Ero1β oxidase activity is regulated by long-range disulfide bonds and that Cys130 plays a critical role in feedback regulation. Compared with Ero1α, however, Ero1β is loosely regulated, consistent with its role as a more active oxidase when massive oxidative power is required.
在真核生物中，二硫键在内质网中形成，这一过程由 Ero1（内质网氧化还原酶 1）氧化酶/PDI（蛋白质二硫键异构酶）系统协助完成。哺乳动物有两个 ERO1 基因，分别编码 Ero1α 和 Ero1β 蛋白。Ero1β 在专业分泌组织中持续表达，并在未折叠蛋白反应期间被诱导。在本工作中，我们发现重组人 Ero1β 在酶促实验中的活性是 Ero1α 的两倍。Ero1β 比其他 PDI 家族成员更有效地氧化 PDI，并通过 PDI á 结构域中的活性位点优先驱动氧化蛋白折叠。我们的结果表明，Ero1β 氧化酶活性受到长程二硫键的调控，并且 Cys130 在反馈调控中起着关键作用。然而，与 Ero1α 相比，Ero1β 的调控较为宽松，这与其在需要大量氧化能力时作为更活跃的氧化酶的作用一致。
