Two Endoplasmic Reticulum PDI Peroxidases Increase the Efficiency of the Use of Peroxide during Disulfide Bond Formation
Two Endoplasmic Reticulum PDI Peroxidases Increase the Efficiency of the Use of Peroxide during Disulfide Bond Formation
复制标题
两种内质网 PDI 过氧化物酶提高二硫键形成过程中过氧化物的使用效率
DOI：
10.1016/j.jmb.2010.12.039
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发表时间：
2011-02-25
影响因子：
5.6
通讯作者：
Ruddock, Lloyd W.
中科院分区：
文献类型：
--
作者：
Nguyen, Van Dat;Saaranen, Mirva J.;Ruddock, Lloyd W.
巯基氧化酶Ero1家族在内质网上形成二硫键的同时，还伴随有过氧化氢的形成。由于分泌细胞可以制造大量含有二硫键的蛋白质，这种活性氧物种的产生可能会产生潜在的致命后果。在这里，我们证明了被标记为分泌型谷胱甘肽过氧化物酶的两种人类蛋白，GPx7和GPx8，实际上是内质网驻留蛋白二硫键异构体过氧化物酶。在体外，将GPx7或GPx8与蛋白质二硫键异构酶和过氧化氢一起添加到折叠蛋白质中，可以有效地氧化还原变性蛋白质的复性。此外，GPx7和GPx8在体内都与Ero1α相互作用，而GPx7在体外显著增加Ero1α的耗氧量。因此，GPx7和GPx8可能代表了一条生产利用Ero1α在二硫键形成过程中产生的过氧化氢的新途径。(C)2011爱思唯尔有限公司。保留所有权利。
Disulfide bond formation in the endoplasmic reticulum by the sulfhydryl oxidase Ero1 family is thought to be accompanied by the concomitant formation of hydrogen peroxide. Since secretory cells can make substantial amounts of proteins that contain disulfide bonds, the production of this reactive oxygen species could have potentially lethal consequences. Here, we show that two human proteins, GPx7 and GPx8, labeled as secreted glutathione peroxidases, are actually endoplasmic reticulum-resident protein disulfide isomerase peroxidases. In vitro, the addition of GPx7 or GPx8 to a folding protein along with protein disulfide isomerase and peroxide enables the efficient oxidative refolding of a reduced denatured protein. Furthermore, both GPx7 and GPx8 interact with Ero1 alpha in vivo, and GPx7 significantly increases oxygen consumption by Ero1 alpha in vitro. Hence, GPx7 and GPx8 may represent a novel route for the productive use of peroxide produced by Ero1 alpha during disulfide bond formation. (C) 2011 Elsevier Ltd. All rights reserved.