Protein Disulfide Isomerase Serves as a Molecular Chaperone to Maintain Estrogen Receptor α Structure and Function

2006 ◽  
Vol 20 (9) ◽  
pp. 1982-1995 ◽  
Author(s):  
Jennifer R. Schultz-Norton ◽  
W. Hayes McDonald ◽  
John R. Yates ◽  
Ann M. Nardulli
Keyword(s):  
Estrogen Receptor ◽  
Molecular Chaperone ◽  
Protein Disulfide Isomerase ◽  
Estrogen Receptor Α ◽  
Structure And Function ◽  
Disulfide Isomerase ◽  
And Function ◽  
Protein Disulfide

A unique leucine-valine adhesive motif supports structure and function of protein disulfide isomerase P5 via dimerization

Structure ◽  
2021 ◽  
Author(s):  
Masaki Okumura ◽  
Shingo Kanemura ◽  
Motonori Matsusaki ◽  
Misaki Kinoshita ◽  
Tomohide Saio ◽  
...  
Keyword(s):  
Protein Disulfide Isomerase ◽  
Structure And Function ◽  
Disulfide Isomerase ◽  
And Function ◽  
Protein Disulfide

scholarly journals Ero1-Mediated Reoxidation of Protein Disulfide Isomerase Accelerates the Folding of Cone Snail Toxins

2018 ◽  
Vol 19 (11) ◽  
pp. 3418 ◽  
Author(s):  
Henrik O’Brien ◽  
Shingo Kanemura ◽  
Masaki Okumura ◽  
Robert Baskin ◽  
Pradip Bandyopadhyay ◽  
...  
Keyword(s):  
Protein Disulfide Isomerase ◽  
Venom Gland ◽  
Cone Snail ◽  
Disulfide Isomerase ◽  
Folding Rates ◽  
Cone Snails ◽  
And Function ◽  
Protein Disulfide ◽  
Insight Into

Disulfide-rich peptides are highly abundant in nature and their study has provided fascinating insight into protein folding, structure and function. Venomous cone snails belong to a group of organisms that express one of the largest sets of disulfide-rich peptides (conotoxins) found in nature. The diversity of structural scaffolds found for conotoxins suggests that specialized molecular adaptations have evolved to ensure their efficient folding and secretion. We recently showed that canonical protein disulfide isomerase (PDI) and a conotoxin-specific PDI (csPDI) are ubiquitously expressed in the venom gland of cone snails and play a major role in conotoxin folding. Here, we identify cone snail endoplasmic reticulum oxidoreductin-1 (Conus Ero1) and investigate its role in the oxidative folding of conotoxins through reoxidation of cone snail PDI and csPDI. We show that Conus Ero1 preferentially reoxidizes PDI over csPDI, suggesting that the reoxidation of csPDI may rely on an Ero1-independent molecular pathway. Despite the preferential reoxidation of PDI over csPDI, the combinatorial effect of Ero1 and csPDI provides higher folding yields than Ero1 and PDI. We further demonstrate that the highest in vitro folding rates of two model conotoxins are achieved when all three enzymes are present, indicating that these enzymes may act synergistically. Our findings provide new insight into the generation of one of the most diverse classes of disulfide-rich peptides and may improve current in vitro approaches for the production of venom peptides for pharmacological studies.

scholarly journals S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen ReceptorαStability and Function

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Xiong ◽  
Yefim Manevich ◽  
Kenneth D. Tew ◽  
Danyelle M. Townsend
Keyword(s):  
Protein Disulfide Isomerase ◽  
Estrogen Receptor Alpha ◽  
Redox Regulation ◽  
Gene Products ◽  
Disulfide Isomerase ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
And Function ◽  
Protein Response ◽  
Protein Disulfide

S-Glutathionylation of cysteine residues within target proteins is a posttranslational modification that alters structure and function. We have shown that S-glutathionylation of protein disulfide isomerase (PDI) disrupts protein folding and leads to the activation of the unfolded protein response (UPR). PDI is a molecular chaperone for estrogen receptor alpha(ERα). Our present data show in breast cancer cells that S-glutathionylation of PDI interferes with its chaperone activity and abolishes its capacity to form a complex withERα. Such drug treatment also reverses estradiol-induced upregulation of c-Myc, cyclinD1, andP21Cip, gene products involved in cell proliferation. Expression of an S-glutathionylation refractory PDI mutant diminishes the toxic effects of PABA/NO. Thus, redox regulation of PDI causes its S-glutathionylation, thereby mediating cell death through activation of the UPR and abrogation ofERαstability and signaling.

scholarly journals N-glycosylation of the protein disulfide isomerase Pdi1 ensuresUstilago maydisvirulence

2019 ◽  
Author(s):  
Miriam Marín-Menguiano ◽  
Ismael Moreno-Sánchez ◽  
Ramón R. Barrales ◽  
Alfonso Fernández-Álvarez ◽  
José Ignacio Ibeas
Keyword(s):  
Virulence Factors ◽  
Protein Disulfide Isomerase ◽  
Ustilago Maydis ◽  
Infection Process ◽  
Protein Glycosylation ◽  
Disulfide Isomerase ◽  
And Function ◽  
Protein Disulfide ◽  
Corn Smut

AbstractFungal pathogenesis depends on accurate secretion and location of virulence factors which drive host colonization. Protein glycosylation is a common posttranslational modification of cell wall components and other secreted factors, typically required for correct protein localization, secretion and function. Thus, the absence of glycosylation is associated with animal and plant pathogen avirulence. While the relevance of protein glycosylation for pathogenesis has been well established, the main glycoproteins responsible for the loss of virulence observed in glycosylation-defective fungi have not been identified. Here, we devise a proteomics approach to identify such proteins and use it to demonstrate a role for the highly conserved protein disulfide isomerase Pdi1 in virulence. We show that efficient Pdi1 N-glycosylation, which promotes folding into the correct protein conformation, is required for full pathogenic development of the corn smut fungusUstilago maydis. Remarkably, the observed virulence defects are reminiscent of those seen in glycosylation-defective cells suggesting that the N-glycosylation of Pdi1 is necessary for the full secretion of virulence factors. All these observations, together with the fact that Pdi1 protein and RNA expression levels rise upon virulence program induction, suggest that Pdi1 glycosylation is a crucial event for pathogenic development inU. maydis. Our results provide new insights into the role of glycosylation in fungal pathogenesis.Author summaryFungal pathogens require virulence factors to be properly secreted and localized to guarantee complete infection. In common with many proteins, virulence factors must be post-translationally modified by glycosylation for normal localization, secretion and function. This is especially important for virulence factors, which are mainly comprised of cell wall and secreted proteins. Aberrant glycosylation leads to a loss of virulence in both animal and plant pathogenic fungi. We have previously demonstrated that glycosylation is important for virulence of the corn smut fungus,Ustilago maydis. However, the glycoproteins involved and their specific roles in the infection process have not yet been reported. Here, we describe a proteomic assay designed to identify glycoproteins involved in plant infection. Using this method, we define the role of Pdi1 protein disulfide isomerase in virulence. Interestingly, abolishing Pdi1 N-glycosylation mimics Δpdi1defects observed during infection, suggesting that Pdi1 N-glycosylation is required for the secretion of virulence factors. We hypothesize that Pdi1 N-glycosylation is crucial for maintaining proper effector protein folding during the infection process, especially in the harsh conditions found inside the maize plant.

scholarly journals Protein Disulfide Isomerase, a Component of the Estrogen Receptor Complex, Is Associated with Chlamydia trachomatis Serovar E Attached to Human Endometrial Epithelial Cells

2002 ◽  
Vol 70 (7) ◽  
pp. 3413-3418 ◽  
Author(s):  
C. H. Davis ◽  
J. E. Raulston ◽  
P. B. Wyrick
Keyword(s):  
Estrogen Receptor ◽  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Host Cell ◽  
Protein Disulfide Isomerase ◽  
Host Cells ◽  
Receptor Complex ◽  
Disulfide Isomerase ◽  
Protein Disulfide ◽  
Endometrial Epithelial Cells

ABSTRACT Chlamydia trachomatis serovar E, the leading bacterial agent responsible for sexually transmitted diseases, is required to invade genital epithelial cells for its growth and survival, yet little is known about the adhesin-receptor interactions promoting its entry. In contrast, much has been published on the heparan sulfate receptor for binding C. trachomatis L2 elementary bodies (EBs) prior to entry into HeLa cells. Using a different experimental approach in which a biotinylated apical membrane protein receptor(s) attached to EB at 4°C was stripped off the surface of polarized HEC-1B cells and immunoprecipitated with polyclonal anti-EB antibodies, an ∼55-kDa protein was reproducibly detected by enhanced chemiluminescence and two-dimensional gel electrophoresis. Matrix-assisted laser desorption ionization mass-spectrometry sequence analysis revealed the 55-kDa protein to be protein disulfide isomerase (PDI), a member of the estrogen receptor complex which carries out thiol-disulfide exchange reactions at infected host cell surfaces. Exposure of HEC-1B cells during EB attachment (1.5 to 2 h) to three different inhibitors of PDI reductive reactions—(i) the thiol-alkylating reagent DTNB (5,5′-dithiobis[2-nitrobenzoic acid]), (ii) bacitracin, and (iii) anti-PDI antibodies—resulted in reduced chlamydial infectivity. Since (i) C. trachomatis serovar E attachment to estrogen-dominant primary human endometrial epithelial cells is dramatically enhanced and (ii) productive entry into and infectivity of EB in host cells is dependent on reduction of EB cross-linked outer membrane proteins at the host cell surface, these data provide some preliminary evidence for an intriguing new potential receptor candidate for further analysis of luminal C. trachomatis serovar E entry.

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