scholarly journals Distinct roles and actions of protein disulfide isomerase family enzymes in catalysis of nascent-chain disulfide bond formation

iScience ◽  
2021 ◽  
pp. 102296
Author(s):  
Chihiro Hirayama ◽  
Kodai Machida ◽  
Kentaro Noi ◽  
Tadayoshi Murakawa ◽  
Masaki Okumura ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Protein Disulfide Isomerase ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Disulfide Isomerase ◽  
Nascent Chain ◽  
Protein Disulfide ◽  
Protein Disulfide Isomerase Family

scholarly journals A di-arginine motif contributes to the ER localization of the type I transmembrane ER oxidoreductase TMX4

2009 ◽  
Vol 425 (1) ◽  
pp. 195-208 ◽  
Author(s):  
Doris Roth ◽  
Emily Lynes ◽  
Jan Riemer ◽  
Henning G. Hansen ◽  
Nils Althaus ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Disulfide Isomerase ◽  
Bond Formation ◽  
Living Cells ◽  
Type I ◽  
Disulfide Bond Formation ◽  
Reporter Protein ◽  
Disulfide Isomerase ◽  
Protein Disulfide ◽  
Protein Disulfide Isomerase Family

The thiol-disulfide oxidoreductases of the PDI (protein disulfide isomerase) family assist in disulfide-bond formation in the ER (endoplasmic reticulum). In the present study, we have shown that the previously uncharacterized PDI family member TMX4 (thioredoxin-like transmembrane 4) is an N-glycosylated type I membrane protein that localizes to the ER. We also demonstrate that TMX4 contains a single ER-luminal thioredoxin-like domain, which, in contrast with similar domains in other PDIs, is mainly oxidized in living cells. The TMX4 transcript displays a wide tissue distribution, and is strongly expressed in melanoma cells. Unlike many type I membrane proteins, TMX4 lacks a typical C-terminal di-lysine retrieval signal. Instead, the cytoplasmic tail has a conserved di-arginine motif of the RXR type. We show that mutation of the RQR sequence in TMX4 to KQK interferes with ER localization of the protein. Moreover, whereas the cytoplasmic region of TMX4 confers ER localization to a reporter protein, the KQK mutant of the same protein redistributes to the cell surface. Overall, features not commonly found in other PDIs characterize TMX4 and suggest unique functional properties of the protein.

Disulfide bond formation in refolding of thermophilic fungal protein disulfide isomerase

2001 ◽  
Vol 91 (6) ◽  
pp. 596-598 ◽  
Author(s):  
Takushi Harada ◽  
Eiji Kurimoto ◽  
Kenrou Tokuhiro ◽  
Osamu Asami ◽  
Tomoya Sakai ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Protein Disulfide Isomerase ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Disulfide Isomerase ◽  
Fungal Protein ◽  
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.

Carbohydrates Facilitate Correct Disulfide Bond Formation and Folding of Rotavirus VP7

1998 ◽  
Vol 72 (5) ◽  
pp. 3887-3892 ◽  
Author(s):  
Ali Mirazimi ◽  
Lennart Svensson
Keyword(s):  
Disulfide Bond ◽  
Protein Disulfide Isomerase ◽  
Bond Formation ◽  
Brefeldin A ◽  
Disulfide Bond Formation ◽  
Disulfide Isomerase ◽  
Major Function ◽  
Reducing Conditions ◽  
Vp7 Protein ◽  
Protein Disulfide

ABSTRACT It is well established that glycosylation is essential for assembly of enveloped viruses, but no information is yet available as to the function of carbohydrates on the nonenveloped but glycosylated rotavirus. We show that tunicamycin and, more pronouncedly, a combination of tunicamycin and brefeldin A treatment caused misfolding of the luminal VP7 protein, leading to interdisulfide bond aggregation. While formation of VP7 aggregates could be prevented under reducing conditions, they reoccurred in less than 30 min after a shift to an oxidizing milieu. Furthermore, while glycosylated VP7 interacted during maturation with protein disulfide isomerase, nonglycosylated VP7 did not, suggesting that glycosylation is a prerequisite for protein disulfide isomerase interaction. While native NSP4, which does not possess S-S bonds, was not dependent on N-linked glycosylation or on protein disulfide isomerase assistance for maturation, nonglycosylated NSP4 was surprisingly found to interact with protein disulfide isomerase, further suggesting that protein disulfide isomerase can act both as an enzyme and as a chaperone. In conclusion, our data suggest that the major function of carbohydrates on VP7 is to facilitate correct disulfide bond formation and protein folding.

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