scholarly journals Organocatalysts of oxidative protein folding inspired by protein disulfide isomerase

2014 ◽  
Vol 12 (43) ◽  
pp. 8598-8602 ◽  
Author(s):  
John C. Lukesh III ◽  
Kristen A. Andersen ◽  
Kelly K. Wallin ◽  
Ronald T. Raines
Keyword(s):  
Protein Folding ◽  
Disulfide Bonds ◽  
Protein Disulfide Isomerase ◽  
Native Protein ◽  
Disulfide Isomerase ◽  
Oxidative Protein Folding ◽  
Hydrophobic Moiety ◽  
Protein Disulfide Bonds ◽  
Protein Disulfide

Organocatalysts derived from ethylenetriamine and containing a hydrophobic moiety effect the isomerization of non-native protein disulfide bonds to native ones.

scholarly journals Non-native proteins inhibit the ER oxidoreductin 1 (Ero1)–protein disulfide-isomerase relay when protein folding capacity is exceeded

2020 ◽  
Vol 295 (26) ◽  
pp. 8647-8655 ◽  
Author(s):  
Antti Moilanen ◽  
Lloyd W. Ruddock
Keyword(s):  
Protein Folding ◽  
Cross Talk ◽  
Protein Disulfide Isomerase ◽  
Feedback Inhibition ◽  
Inhibition Mechanism ◽  
Disulfide Isomerase ◽  
Unfolded Protein ◽  
Oxidative Protein Folding ◽  
Native Proteins ◽  
Protein Disulfide

Protein maturation in the endoplasmic reticulum (ER) depends on a fine balance between oxidative protein folding and quality control mechanisms, which together ensure high-capacity export of properly folded proteins from the ER. Oxidative protein folding needs to be regulated to avoid hyperoxidation. The folding capacity of the ER is regulated by the unfolded protein response (UPR) and ER-associated degradation (ERAD). The UPR is triggered by unfolded protein stress and leads to up-regulation of cellular components such as chaperones and folding catalysts. These components relieve stress by increasing folding capacity and up-regulating ERAD components that remove non-native proteins. Although oxidative protein folding and the UPR/ERAD pathways each are well-understood, very little is known about any direct cross-talk between them. In this study, we carried out comprehensive in vitro activity and binding assays, indicating that the oxidative protein folding relay formed by ER oxidoreductin 1 (Ero1), and protein disulfide-isomerase can be inactivated by a feedback inhibition mechanism involving unfolded proteins and folding intermediates when their levels exceed the folding capacity of the system. This mechanism allows client proteins to remain mainly in the reduced state and thereby minimizes potential futile oxidation–reduction cycles and may also enhance ERAD, which requires reduced protein substrates. Relief from excess levels of non-native proteins by increasing the levels of folding factors removed the feedback inhibition. These results reveal regulatory cross-talk between the oxidative protein folding and UPR and ERAD pathways.

Cigarette smoking affects oxidative protein folding in endoplasmic reticulum by modifying protein disulfide isomerase

2012 ◽  
Vol 27 (3) ◽  
pp. 965-977 ◽  
Author(s):  
Harshavardhan Kenche ◽  
Catherine J. Baty ◽  
Kokilavani Vedagiri ◽  
Steven D. Shapiro ◽  
Anna Blumental‐Perry
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Cigarette Smoking ◽  
Protein Disulfide Isomerase ◽  
Disulfide Isomerase ◽  
Oxidative Protein Folding ◽  
Protein Disulfide

scholarly journals The Contributions of Protein Disulfide Isomerase and Its Homologues to Oxidative Protein Folding in the Yeast Endoplasmic Reticulum

2004 ◽  
Vol 279 (48) ◽  
pp. 49780-49786 ◽  
Author(s):  
Ruoyu Xiao ◽  
Bonney Wilkinson ◽  
Anton Solovyov ◽  
Jakob R. Winther ◽  
Arne Holmgren ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Protein Disulfide Isomerase ◽  
Disulfide Isomerase ◽  
Oxidative Protein Folding ◽  
Protein Disulfide

scholarly journals PDI-Regulated Disulfide Bond Formation in Protein Folding and Biomolecular Assembly

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 171
Author(s):  
Jiahui Fu ◽  
Jihui Gao ◽  
Zhongxin Liang ◽  
Dong Yang
Keyword(s):  
Protein Folding ◽  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Protein Disulfide Isomerase ◽  
Bond Formation ◽  
Molecular Assembly ◽  
Disulfide Bond Formation ◽  
Disulfide Isomerase ◽  
Biomolecular Assembly ◽  
Protein Disulfide

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.

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