Recycling of peroxiredoxin IV provides a novel pathway for disulphide formation in the endoplasmic reticulum.-猫眼课题宝

DOI：

10.1038/emboj.2010.273

发表时间：

2010-12-15

期刊：

EMBO JOURNAL

影响因子：

11.4

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Tavender, Timothy J.;Springate, Jennifer J.;Bulleid, Neil J.

关键词：

disulphide formation hydrogen peroxide peroxiredoxin IV protein disulphide isomerase protein folding

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018787/?report=classic

Ero1被认为是唯一的氧化酶，介导的蛋白质二硫化物异构酶（PDI）的再氧化过程中的氧化蛋白质折叠的ER。这项研究表明，peroxiredoxin IV也可以直接氧化PDI家族成员，从而作为第二个来源的氧化等价物的二硫键形成的ER。内质网（ER）中的二硫化物形成由蛋白质二硫化物异构酶（PDI）家族的成员催化。这些酶可以被黄素蛋白ER氧化还原素1（Ero 1）氧化，其将二硫化物形成与氧的还原偶联以形成过氧化氢（H2O2）。产生的H2O2可以通过ER定位的过氧化物氧还蛋白IV（PrxIV）代谢。PrxIV的连续催化活性取决于活性位点内二硫化物的还原以形成游离硫醇，其然后可以与H2O2反应。在这里，我们证明了PDI家族的几个成员能够直接还原这种PrxIV二硫化物，并在此过程中被氧化。此外，我们表明，改变这些蛋白质的细胞内表达的ER影响的效率与PrxIV可以回收。通过PrxIV氧化PDI家族成员是一种高效的过程，并证明了通过H2O2的氧化如何与二硫化物形成相结合。因此，PrxIV对PDI的氧化可以提高Ero 1形成二硫化物的效率，并且还允许通过H2O2的替代来源形成二硫化物。

Ero1 is thought to be the only oxidase that mediates the re-oxidation of protein disulphide isomerases (PDIs) during oxidative protein folding in the ER. This study reveals that peroxiredoxin IV can also directly oxidize PDI-family members and thus act as a second source of oxidizing equivalents for disulphide-bond formation in the ER. Disulphide formation in the endoplasmic reticulum (ER) is catalysed by members of the protein disulphide isomerase (PDI) family. These enzymes can be oxidized by the flavoprotein ER oxidoreductin 1 (Ero1), which couples disulphide formation with reduction of oxygen to form hydrogen peroxide (H2O2). The H2O2 produced can be metabolized by ER-localized peroxiredoxin IV (PrxIV). Continuous catalytic activity of PrxIV depends on reduction of a disulphide within the active site to form a free thiol, which can then react with H2O2. Here, we demonstrate that several members of the PDI family are able to directly reduce this PrxIV disulphide and in the process become oxidized. Furthermore, we show that altering cellular expression of these proteins within the ER influences the efficiency with which PrxIV can be recycled. The oxidation of PDI family members by PrxIV is a highly efficient process and demonstrates how oxidation by H2O2 can be coupled to disulphide formation. Oxidation of PDI by PrxIV may therefore increase efficiency of disulphide formation by Ero1 and also allows disulphide formation via alternative sources of H2O2.