Okumura Masaki, Kadokura Hiroshi, Inaba Kenji
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan.
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan.
Free Radic Biol Med. 2015 Jun;83:314-22. doi: 10.1016/j.freeradbiomed.2015.02.010. Epub 2015 Feb 17.
The endoplasmic reticulum (ER) is an essential cellular compartment in which an enormous number of secretory and cell surface membrane proteins are synthesized and subjected to cotranslational or posttranslational modifications, such as glycosylation and disulfide bond formation. Proper maintenance of ER protein homeostasis (sometimes termed proteostasis) is essential to avoid cellular stresses and diseases caused by abnormal proteins. Accumulating knowledge of cysteine-based redox reactions catalyzed by members of the protein disulfide isomerase (PDI) family has revealed that these enzymes play pivotal roles in productive protein folding accompanied by disulfide formation, as well as efficient ER-associated degradation accompanied by disulfide reduction. Each of PDI family members forms a protein-protein interaction with a preferential partner to fulfill a distinct function. Multiple redox pathways that utilize PDIs appear to function synergistically to attain the highest quality and productivity of the ER, even under various stress conditions. This review describes the structures, physiological functions, and cooperative actions of several essential PDIs, and provides important insights into the elaborate proteostatic mechanisms that have evolved in the extremely active and stress-sensitive ER.
内质网（ER）是一个重要的细胞区室，大量分泌蛋白和细胞表面膜蛋白在此合成，并经历共翻译或翻译后修饰，如糖基化和二硫键形成。内质网蛋白质稳态（有时称为蛋白质平衡）的适当维持对于避免由异常蛋白质引起的细胞应激和疾病至关重要。对蛋白质二硫键异构酶（PDI）家族成员催化的基于半胱氨酸的氧化还原反应的认识不断积累，揭示了这些酶在伴随着二硫键形成的有效蛋白质折叠以及伴随着二硫键还原的高效内质网相关降解中发挥着关键作用。每个PDI家族成员都与一个优先伙伴形成蛋白质-蛋白质相互作用，以履行独特的功能。即使在各种应激条件下，利用PDI的多种氧化还原途径似乎也能协同发挥作用，以实现内质网的最高质量和生产力。本综述描述了几种重要PDI的结构、生理功能和协同作用，并为在极其活跃且对压力敏感的内质网中进化出的精细蛋白质平衡机制提供了重要见解。
