Disulfide bonds play essential roles in the folding of secretory and plasma membrane proteins in the endoplasmic reticulum (ER). In eukaryotes, protein disulfide isomerase (PDI) is an enzyme catalyzing the disulfide bond formation and isomerization in substrates. The Arabidopsis (Arabidopsis thaliana) genome encodes diverse PDIs including structurally distinct subgroups PDI-L and PDI-M/S. It remains unclear how these AtPDIs function to catalyze the correct disulfide formation. We found that one Arabidopsis ER oxidoreductin-1 (Ero1), AtERO1, can interact with multiple PDIs. PDI-L members AtPDI2/5/6 mainly serve as an isomerase, while PDI-M/S members AtPDI9/10/11 are more efficient in accepting oxidizing equivalents from AtERO1 and catalyzing disulfide bond formation. Accordingly, the pdi9/10/11 triple mutant exhibited much stronger inhibition than pdi1/2/5/6 quadruple mutant under dithiothreitol treatment, which caused disruption of disulfide bonds in plant proteins. Furthermore, AtPDI2/5 work synergistically with PDI-M/S members in relaying disulfide bonds from AtERO1 to substrates. Our findings reveal the distinct but overlapping roles played by two structurally different AtPDI subgroups in oxidative protein folding in the ER.

中文翻译：

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两个蛋白质二硫键异构酶亚群协同作用催化氧化蛋白质折叠

二硫键在内质网 (ER) 中的分泌和质膜蛋白折叠中起重要作用。在真核生物中，蛋白质二硫键异构酶 (PDI) 是一种催化底物中二硫键形成和异构化的酶。拟南芥 (Arabidopsis thaliana) 基因组编码不同的 PDI，包括结构上不同的亚组 PDI-L 和 PDI-M/S。目前尚不清楚这些 AtPDI 如何发挥催化正确二硫化物形成的作用。我们发现一种拟南芥 ER oxidoreductin-1 (Ero1) AtERO1 可以与多种 PDI 相互作用。PDI-L 成员 AtPDI2/5/6 主要用作异构酶，而 PDI-M/S 成员 AtPDI9/10/11 在接受来自 AtERO1 的氧化等价物和催化二硫键形成方面更有效。因此，pdi9/10/11 三重突变体在二硫苏糖醇处理下表现出比 pdi1/2/5/6 四重突变体更强的抑制作用，导致植物蛋白中二硫键的破坏。此外，AtPDI2/5 与 PDI-M/S 成员协同工作，将 AtERO1 的二硫键传递到底物。我们的研究结果揭示了两个结构不同的 AtPDI 亚群在 ER 中的氧化蛋白折叠中所起的不同但重叠的作用。