Sevier Carolyn S, Kaiser Chris A
Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, USA.
Antioxid Redox Signal. 2006 May-Jun;8(5-6):797-811. doi: 10.1089/ars.2006.8.797.
Two pathways for the formation of biosynthetic protein disulfide bonds have been characterized in the endoplasmic reticulum (ER) of eukaryotes. In the major pathway, the membrane-associated flavoprotein Ero1 generates disulfide bonds for transfer to protein disulfide isomerase (PDI), which is responsible for directly introducing disulfide bonds into secretory proteins. In a minor fungal-specific protein oxidation pathway, the membrane-associated flavoprotein Erv2 can catalyze disulfide bond formation via the transfer of oxidizing equivalents to PDI. Genomic sequencing has revealed an abundance of enzymes sharing homology with Ero1, Erv2, or PDI. Herein the authors discuss the functional, mechanistic, and potential structural similarities between these homologs and the core enzymes of the characterized ER oxidation pathways. In addition they speculate about the possible differences between these enzymes that may explain why the cell contains multiple proteins dedicated to a single process. Finally, the eukaryotic ER protein oxidation and reduction pathways are compared to the corresponding prokaryotic periplasmic pathways, to highlight the functional, mechanistic, and structural similarities that exist between the pathways in these two kingdoms despite very low primary sequence homology between the protein and small molecule components.
在真核生物的内质网（ER）中，已鉴定出生物合成蛋白质二硫键形成的两条途径。在主要途径中，与膜相关的黄素蛋白Ero1产生二硫键并将其转移至蛋白质二硫键异构酶（PDI），后者负责将二硫键直接引入分泌蛋白中。在一条次要的真菌特异性蛋白质氧化途径中，与膜相关的黄素蛋白Erv2可通过将氧化当量转移至PDI来催化二硫键的形成。基因组测序显示，有大量与Ero1、Erv2或PDI具有同源性的酶。本文作者讨论了这些同源物与已鉴定的内质网氧化途径的核心酶之间在功能、机制和潜在结构上的相似性。此外，他们推测了这些酶之间可能存在的差异，这些差异或许可以解释为何细胞中含有多种专门用于单一过程的蛋白质。最后，将真核生物内质网蛋白质氧化和还原途径与相应的原核生物周质途径进行比较，以突出这两个界别中途径之间存在的功能、机制和结构相似性，尽管蛋白质和小分子成分之间的一级序列同源性非常低。
