Chaperone Activity of DsbC

Chen, Jun; Song, Jiu-li; Zhang, Sen; Wang, Yan; Cui, Dafu; Wang, Chih-chen

doi:10.1074/jbc.274.28.19601

Cited by 163 publications

(110 citation statements)

References 34 publications

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“…In the analyses shown here, ERD10 and ERD14 demonstrated marked effects on the prevention of aggregation/deactivation of protein substrates. A comparison of related data published in the literature, such as for periplasmic disulfide isomerase of Gram-negative bacteria (DsbC; Chen et al, 1999), a-synuclein (Kim et al, 2000;Souza et al, 2000;Ahn et al, 2006), HSP90 (Minami et al, 2001), or tubulin (Guha et al, 1998), makes it safe to conclude that ERD10 and ERD14 are chaperones of commensurate potency to previously described representatives of this functional class. The significance of the effect is underlined by the fact that it far exceeds that of BSA and in several cases is commensurate with, or even exceeds, that exerted by HSP90.…”

Section: Discussionmentioning

confidence: 99%

Chaperone Activity of ERD10 and ERD14, Two Disordered Stress-Related Plant Proteins

et al. 2008

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ERD10 and ERD14 (for early response to dehydration) proteins are members of the dehydrin family that accumulate in response to abiotic environmental stresses, such as high salinity, drought, and low temperature, in Arabidopsis (Arabidopsis thaliana). Whereas these proteins protect cells against the consequences of dehydration, the exact mode(s) of their action remains poorly understood. Here, detailed evidence is provided that ERD10 and ERD14 belong to the family of intrinsically disordered proteins, and it is shown in various assays that they act as chaperones in vitro. ERD10 and ERD14 are able to prevent the heat-induced aggregation and/or inactivation of various substrates, such as lysozyme, alcohol dehydrogenase, firefly luciferase, and citrate synthase. It is also demonstrated that ERD10 and ERD14 bind to acidic phospholipid vesicles without significantly affecting membrane fluidity. Membrane binding is strongly influenced by ionic strength. Our results show that these intrinsically disordered proteins have chaperone activity of rather wide substrate specificity and that they interact with phospholipid vesicles through electrostatic forces. We suggest that these findings provide the rationale for the mechanism of how these proteins avert the adverse effects of dehydration stresses.

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Section: Discussionmentioning

confidence: 99%

Chaperone Activity of ERD10 and ERD14, Two Disordered Stress-Related Plant Proteins

et al. 2008

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“…Because misoxidized substrates of DsbC are likely to be misfolded with core hydrophobic residues surface-exposed, the hydrophobic cleft of DsbC might mediate the interaction between the misfolded substrate protein and cysteines 98 -101. Furthermore, DsbC possesses chaperone activity that is independent of cysteines 98 and 101 (12).…”

mentioning

confidence: 99%

The Nonconsecutive Disulfide Bond of Escherichia coli Phytase (AppA) Renders It Dependent on the Protein-disulfide Isomerase, DsbC

Berkmen¹,

Boyd

Beckwith

2005

Journal of Biological Chemistry

120

119

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The formation of protein disulfide bonds in the Escherichia coli periplasm by the enzyme DsbA is an inaccurate process. Many eukaryotic proteins with nonconsecutive disulfide bonds expressed in E. coli require an additional protein for proper folding, the disulfide bond isomerase DsbC. Here we report studies on a native E. coli periplasmic acid phosphatase, phytase (AppA), which contains three consecutive and one nonconsecutive disulfide bonds. We show that AppA requires DsbC for its folding. However, the activity of an AppA mutant lacking its nonconsecutive disulfide bond is DsbC-independent. An AppA homolog, Agp, a periplasmic acid phosphatase with similar structure, lacks the nonconsecutive disulfide bond but has the three consecutive disulfide bonds found in AppA. The consecutively disulfide-bonded Agp is not dependent on DsbC but is rendered dependent by engineering into it the conserved nonconsecutive disulfide bond of AppA. Taken together, these results provide support for the proposal that proteins with nonconsecutive disulfide bonds require DsbC for full activity and that disulfide bonds are formed predominantly during translocation across the cytoplasmic membrane.Disulfide bonds between cysteine residues make an important contribution to the folding pathway and stability of many proteins. Early in vitro studies on protein folding showed that the protein RNase when denatured and its disulfide bonds reduced could refold into an active enzyme with the correct disulfide bonds formed (1). Although these results indicated that the information necessary for the proper folding of proteins was intrinsic to the amino acid sequence, the rate of disulfide bond formation in these experiments was much slower than the rates observed in living cells, and the yield of active enzyme was low. The low yields of properly folded enzyme were attributed to the formation of incorrect disulfide bonds in many of the assembled protein molecules. Thus, the in vitro studies, although remarkably successful, were unable to come close to replicating the rapid kinetics and the accuracy of in vivo disulfide bond formation. To explain this inaccuracy observed in biochemical experiments, Anfinsen and co-workers

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“…The Isomerase Activity of DsbC Is Important for OM Integrity-To test these two hypotheses, we first compared the ability of wild-type DsbC and of a DsbC mutant in which both catalytic cysteine residues are replaced by serine (DsbC SXXS ) to complement the phenotype of the surAdsbC mutant. DsbC SXXS lacks the isomerase activity of DsbC but keeps the chaperone activity of the protein (18). As shown in Fig.…”

Section: Resultsmentioning

confidence: 83%

“…Recently, we discovered that DsbC, together with another thioredoxin-related protein DsbG, also protects single cysteine residues from oxidation by reactive oxygen species present in the periplasm (17). Moreover, as stated above, DsbC exhibits a chaperone activity in vitro and can assist the refolding of denaturated proteins like lysozyme or glyceraldehyde-3-phosphate dehydrogenase (18). The active site cysteine residues are not required for this chaperone activity (19).…”

mentioning

confidence: 99%

The Protein-disulfide Isomerase DsbC Cooperates with SurA and DsbA in the Assembly of the Essential β-Barrel Protein LptD

Denoncin

Vertommen

Paek

et al. 2010

Journal of Biological Chemistry

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The assembly of the ␤-barrel proteins present in the outer membrane (OM) of Gram-negative bacteria is poorly characterized. After translocation across the inner membrane, unfolded ␤-barrel proteins are escorted across the periplasm by chaperones that reside within this compartment. Two partially redundant chaperones, SurA and Skp, are considered to transport the bulk mass of ␤-barrel proteins. We found that the periplasmic disulfide isomerase DsbC cooperates with SurA and the thiol oxidase DsbA in the folding of the essential ␤-barrel protein LptD. LptD inserts lipopolysaccharides in the OM. It is also the only ␤-barrel protein with more than two cysteine residues. We found that surAdsbC mutants, but not skpdsbC mutants, exhibit a synthetic phenotype. They have a decreased OM integrity, which is due to the lack of the isomerase activity of DsbC. We also isolated DsbC in a mixed disulfide complex with LptD. As such, LptD is identified as the first substrate of DsbC that is localized in the OM. Thus, electrons flowing from the cytoplasmic thioredoxin system maintain the integrity of the OM by assisting the folding of one of the most important ␤-barrel proteins. The outer membrane (OM)4 is a complex macromolecular structure that is essential for the viability of Gram-negative bacteria and serves as a permeability barrier against hydrophobic antibiotics. It is a unique asymmetric lipid bilayer with phospholipids forming the inner leaflet and lipopolysaccharides (LPS) forming the outer leaflet. The proteins that are present in the OM are either lipoproteins that are anchored to the inner leaflet via a lipid moiety or ␤-barrel proteins that are integral membrane proteins. The mechanisms that govern the assembly of the OM are poorly understood (1-3). In particular, we have a poor understanding of how the ␤-barrel proteins, which are synthesized in the cytoplasm and translocated unfolded across the inner membrane by the Sec translocon, are then transported across the periplasm and inserted in the OM. According to the most widely accepted model, unfolded ␤-barrel proteins are escorted across the periplasm by soluble periplasmic chaperones that deliver them to an OM multiprotein complex involving the ␤-barrel protein BamA (3, 4). Two partially redundant periplasmic chaperone pathways have been described in the Escherichia coli periplasm (5, 6). The first one involves SurA, a periplasmic prolyl cistrans-isomerase, which is considered as the primary chaperone in the periplasm. SurA has been shown to be involved in the biogenesis of the most abundant ␤-barrel proteins, such as OmpA, OmpF, and OmpC (6, 7), and is the preferred chaperone for the essential protein LptD (previously Imp) (8). The second pathway involves the chaperone Skp and the protease/ chaperone protein DegP. This pathway has been proposed to serve as a backup for SurA, assisting the biogenesis of the proteins that fell off the SurA pathway (6). The fact that surAskp and surAdegP mutants are not viable (5) indicates that cells cannot survive without at least o...

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Chaperone Activity of DsbC

Cited by 163 publications

References 34 publications

Chaperone Activity of ERD10 and ERD14, Two Disordered Stress-Related Plant Proteins

Chaperone Activity of ERD10 and ERD14, Two Disordered Stress-Related Plant Proteins

The Nonconsecutive Disulfide Bond of Escherichia coli Phytase (AppA) Renders It Dependent on the Protein-disulfide Isomerase, DsbC

The Protein-disulfide Isomerase DsbC Cooperates with SurA and DsbA in the Assembly of the Essential β-Barrel Protein LptD

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