scholarly journals Protein-disulfide Isomerase- and Protein Thiol-dependent Dehydroascorbate Reduction and Ascorbate Accumulation in the Lumen of the Endoplasmic Reticulum

2001 ◽  
Vol 276 (12) ◽  
pp. 8825-8828 ◽  
Author(s):  
Gábor Nardai ◽  
László Braun ◽  
Miklós Csala ◽  
Valéria Mile ◽  
Péter Csermely ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Disulfide Isomerase ◽  
Protein Thiol ◽  
Disulfide Isomerase ◽  
Protein Disulfide ◽  
Dehydroascorbate Reduction

scholarly journals Structure-Function Analysis of the Endoplasmic Reticulum Oxidoreductase TMX3 Reveals Interdomain Stabilization of the N-terminal Redox-active Domain

2007 ◽  
Vol 282 (46) ◽  
pp. 33859-33867 ◽  
Author(s):  
Johannes Haugstetter ◽  
Michael Andreas Maurer ◽  
Thomas Blicher ◽  
Martin Pagac ◽  
Gerhard Wider ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Disulfide Isomerase ◽  
Function Analysis ◽  
Transmembrane Protein ◽  
Reduced Form ◽  
Disulfide Isomerase ◽  
Binding Domains ◽  
Redox Active ◽  
Protein Disulfide ◽  
Protein Disulfide Isomerase Family

Disulfide bond formation in the endoplasmic reticulum is catalyzed by enzymes of the protein disulfide-isomerase family that harbor one or more thioredoxin-like domains. We recently discovered the transmembrane protein TMX3, a thiol-disulfide oxidoreductase of the protein disulfide-isomerase family. Here, we show that the endoplasmic reticulum-luminal region of TMX3 contains three thioredoxin-like domains, an N-terminal redox-active domain (named a) followed by two enzymatically inactive domains (b and b′). Using the recombinantly expressed TMX3 domain constructs a, ab, and abb′, we compared structural stability and enzymatic properties. By structural and biophysical methods, we demonstrate that the reduced a domain has features typical of a globular folded domain that is, however, greatly destabilized upon oxidization. Importantly, interdomain stabilization by the b domain renders the a domain more resistant toward chemical denaturation and proteolysis in both the oxidized and reduced form. In combination with molecular modeling studies of TMX3 abb′, the experimental results provide a new understanding of the relationship between the multidomain structure of TMX3 and its function as a redox enzyme. Overall, the data indicate that in addition to their role as substrate and co-factor binding domains, redox-inactive thioredoxin-like domains also function in stabilizing neighboring redox-active domains.

scholarly journals Identification of a Novel Saturable Endoplasmic Reticulum Localization Mechanism Mediated by the C-Terminus of aDictyostelium Protein Disulfide Isomerase

2000 ◽  
Vol 11 (10) ◽  
pp. 3469-3484 ◽  
Author(s):  
Jean Monnat ◽  
Eva M. Neuhaus ◽  
Marius S. Pop ◽  
David M. Ferrari ◽  
Barbara Kramer ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Disulfide Isomerase ◽  
Fluorescent Protein ◽  
Null Mutation ◽  
Disulfide Isomerase ◽  
Isomerase Activity ◽  
C Terminus ◽  
Complementary Action ◽  
Green Fluorescent ◽  
Protein Disulfide

Localization of soluble endoplasmic reticulum (ER) resident proteins is likely achieved by the complementary action of retrieval and retention mechanisms. Whereas the machinery involving the H/KDEL and related retrieval signals in targeting escapees back to the ER is well characterized, other mechanisms including retention are still poorly understood. We have identified a protein disulfide isomerase (Dd-PDI) lacking the HDEL retrieval signal normally found at the C terminus of ER residents in Dictyostelium discoideum. Here we demonstrate that its 57 residue C-terminal domain is necessary for intracellular retention of Dd-PDI and sufficient to localize a green fluorescent protein (GFP) chimera to the ER, especially to the nuclear envelope. Dd-PDI and GFP-PDI57 are recovered in similar cation-dependent complexes. The overexpression of GFP-PDI57 leads to disruption of endogenous PDI complexes and induces the secretion of PDI, whereas overexpression of a GFP-HDEL chimera induces the secretion of endogenous calreticulin, revealing the presence of two independent and saturable mechanisms. Finally, low-level expression of Dd-PDI but not of PDI truncated of its 57 C-terminal residues complements the otherwise lethal yeast TRG1/PDI1 null mutation, demonstrating functional disulfide isomerase activity and ER localization. Altogether, these results indicate that the PDI57 peptide contains ER localization determinants recognized by a conserved machinery present in D. discoideum and Saccharomyces cerevisiae.

The yeast EUG1 gene encodes an endoplasmic reticulum protein that is functionally related to protein disulfide isomerase

1992 ◽  
Vol 12 (10) ◽  
pp. 4601-4611
Author(s):  
C Tachibana ◽  
T H Stevens
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Protein Disulfide Isomerase ◽  
Yeast Cells ◽  
Disulfide Isomerase ◽  
Protein Levels ◽  
Growth Defects ◽  
Endoplasmic Reticulum Protein ◽  
Related Proteins ◽  
Protein Disulfide

The product of the EUG1 gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein with homology to both the mammalian protein disulfide isomerase (PDI) and the yeast PDI homolog encoded by the essential PDI1 gene. Deletion or overexpression of EUG1 causes no growth defects under a variety of conditions. EUG1 mRNA and protein levels are dramatically increased in response to the accumulation of native or unglycosylated proteins in the endoplasmic reticulum. Overexpression of the EUG1 gene allows yeast cells to grow in the absence of the PDI1 gene product. Depletion of the PDI1 protein in Saccharomyces cerevisiae causes a soluble vacuolar glycoprotein to accumulate in its endoplasmic reticulum form, and this phenotype is only partially relieved by the overexpression of EUG1. Taken together, our results indicate that PDI1 and EUG1 encode functionally related proteins that are likely to be involved in interacting with nascent polypeptides in the yeast endoplasmic reticulum.

scholarly journals PDI Family Members as Guides for Client Folding and Assembly

2020 ◽  
Vol 21 (24) ◽  
pp. 9351
Author(s):  
Shingo Kanemura ◽  
Motonori Matsusaki ◽  
Kenji Inaba ◽  
Masaki Okumura
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Viability ◽  
Molecular Chaperones ◽  
Protein Disulfide Isomerase ◽  
Family Members ◽  
Secretory Proteins ◽  
Efficient Production ◽  
Protein Homeostasis ◽  
Disulfide Isomerase ◽  
Protein Disulfide

Complicated and sophisticated protein homeostasis (proteostasis) networks in the endoplasmic reticulum (ER), comprising disulfide catalysts, molecular chaperones, and their regulators, help to maintain cell viability. Newly synthesized proteins inserted into the ER need to fold and assemble into unique native structures to fulfill their physiological functions, and this is assisted by protein disulfide isomerase (PDI) family. Herein, we focus on recent advances in understanding the detailed mechanisms of PDI family members as guides for client folding and assembly to ensure the efficient production of secretory proteins.

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