Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science & Nutritional Engineering, China Agricultural University, 17 East Tsinghua Rd., Beijing 100083, China.
Molecules. 2020 Dec 31;26(1):171. doi: 10.3390/molecules26010171.
Disulfide bonds play a pivotal role in maintaining the natural structures of proteins to ensure their performance of normal biological functions. Moreover, biological molecular assembly, such as the gluten network, is also largely dependent on the intermolecular crosslinking via disulfide bonds. In eukaryotes, the formation and rearrangement of most intra- and intermolecular disulfide bonds in the endoplasmic reticulum (ER) are mediated by protein disulfide isomerases (PDIs), which consist of multiple thioredoxin-like domains. These domains assist correct folding of proteins, as well as effectively prevent the aggregation of misfolded ones. Protein misfolding often leads to the formation of pathological protein aggregations that cause many diseases. On the other hand, glutenin aggregation and subsequent crosslinking are required for the formation of a rheologically dominating gluten network. Herein, the mechanism of PDI-regulated disulfide bond formation is important for understanding not only protein folding and associated diseases, but also the formation of functional biomolecular assembly. This review systematically illustrated the process of human protein disulfide isomerase (hPDI) mediated disulfide bond formation and complemented this with the current mechanism of wheat protein disulfide isomerase (wPDI) catalyzed formation of gluten networks.
二硫键在维持蛋白质的天然结构以确保其正常生物功能方面起着关键作用。此外，生物分子组装，如面筋网络，也在很大程度上依赖于二硫键的分子间交联。在内质网（ER）中，大多数二硫键的形成和重排是由蛋白质二硫键异构酶（PDI）介导的，它由多个硫氧还蛋白样结构域组成。这些结构域有助于蛋白质的正确折叠，并有效地防止错误折叠的蛋白质聚集。蛋白质错误折叠常常导致病理性蛋白质聚集的形成，从而导致许多疾病。另一方面，谷蛋白的聚集和随后的交联对于形成流变学上占主导地位的谷蛋白网络是必需的。在此，PDI 调节的二硫键形成机制不仅对于理解蛋白质折叠和相关疾病很重要，而且对于功能性生物分子组装的形成也很重要。本文系统地阐述了人源蛋白二硫键异构酶（hPDI）介导的二硫键形成过程，并结合当前小麦蛋白二硫键异构酶（wPDI）催化谷蛋白网络形成的机制对此进行了补充。
