Protein disulfide isomerases exploit synergy between catalytic and specific binding domains

Freedman, Robert B.; Klappa, Peter; Ruddock, Lloyd W.

doi:10.1093/embo-reports/kvf035

Cited by 171 publications

(149 citation statements)

References 48 publications

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“…2 For the redox-active a and a domains, it is noteworthy that neither seemed to undergo significant structural changes upon formation of the active-site disulfide bond as judged by far-UV CD spectroscopy (Fig. 3, b and c).…”

Section: Discussionmentioning

confidence: 92%

“…Still, protein disulfide isomerase (PDI), an essential and well characterized ER resident enzyme, is known to interact with various substrates and to catalyze their oxidation, reduction, and isomerization (reviewed in Ref. 2). Recently, it has become evident that PDI obtains the oxidizing equivalents that it uses for oxidation of cysteine thiols from Ero1, a membrane-associated FAD-binding ER protein that transfers electrons from PDI to molecular oxygen (3,4).…”

mentioning

confidence: 99%

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ERp57 Is a Multifunctional Thiol-Disulfide Oxidoreductase

Frickel

Frei

Bouvier

et al. 2004

Journal of Biological Chemistry

179

129

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The thiol-disulfide oxidoreductase ERp57 is a soluble protein of the endoplasmic reticulum and the closest known homologue of protein disulfide isomerase. The protein interacts with the two lectin chaperones calnexin and calreticulin and thereby promotes the oxidative folding of newly synthesized glycoproteins. Here we have characterized several fundamental structural and functional properties of ERp57 in vitro, such as the domain organization, shape, redox potential, and the ability to catalyze different thiol-disulfide exchange reactions. Like protein disulfide isomerase, we find ERp57 to be comprised of four structural domains. The protein has an elongated shape of 3.4 ؎ 0.1 nm in diameter and 16.8 ؎ 0.5 nm in length. The two redox-active a and a domains were determined to have redox potentials of ؊0.167 and ؊0.156 V, respectively. Furthermore, ERp57 was shown to efficiently catalyze disulfide reduction, disulfide isomerization, and dithiol oxidation in substrate proteins. The implications of these findings for the function of the protein in vivo are discussed.

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Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

ERp57 Is a Multifunctional Thiol-Disulfide Oxidoreductase

Frickel

Frei

Bouvier

et al. 2004

Journal of Biological Chemistry

179

129

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“…In addition to BiP/Kar2, various molecular chaperones and folding enzymes such as calnexin and protein disulfide isomerase fulfill many of the complex requirements for protein folding in the ER. Calnexin is a chaperone that is basically specific to N-glycosylated proteins (Williams, 2006), and protein disulfide isomerase promotes the formation and rearrangement of the disulfide bonds (Freedman, 2002;Hosoda et al, 2003). The ER also functions as the quality control compartment of folding proteins (Ellgaard et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Saccharomyces cerevisiaeRot1 Is an Essential Molecular Chaperone in the Endoplasmic Reticulum

Takeuchi

Kohno

2008

MBoC

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Molecular chaperones prevent aggregation of denatured proteins in vitro and are thought to support folding of diverse proteins in vivo. Chaperones may have some selectivity for their substrate proteins, but knowledge of particular in vivo substrates is still poor. We here show that yeast Rot1, an essential, type-I ER membrane protein functions as a chaperone. Recombinant Rot1 exhibited antiaggregation activity in vitro, which was partly impaired by a temperature-sensitive rot1-2 mutation. In vivo, the rot1-2 mutation caused accelerated degradation of five proteins in the secretory pathway via ER-associated degradation, resulting in a decrease in their cellular levels. Furthermore, we demonstrate a physical and probably transient interaction of Rot1 with four of these proteins. Collectively, these results indicate that Rot1 functions as a chaperone in vivo supporting the folding of those proteins. Their folding also requires BiP, and one of these proteins was simultaneously associated with both Rot1 and BiP, suggesting that they can cooperate to facilitate protein folding. The Rot1-dependent proteins include a soluble, type I and II, and polytopic membrane proteins, and they do not share structural similarities. In addition, their dependency on Rot1 appeared different. We therefore propose that Rot1 is a general chaperone with some substrate specificity.

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“…Another distinct family of ER-resident proteins, of which protein disulfide isomerase (PDI) is best documented (21,22), is defined by the presence of thioredoxin-like motifs in their primary structure. PDI promotes oxidative folding of secretory proteins through catalyzing thiol-disulfide exchange reactions including disulfide formation, disulfide reduction, and disulfide isomerization.…”

mentioning

confidence: 99%

JPDI, a Novel Endoplasmic Reticulum-resident Protein Containing Both a BiP-interacting J-domain and Thioredoxin-like Motifs

Hosoda

Kimata

Tsuru

et al. 2003

Journal of Biological Chemistry

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Several endoplasmic reticulum (ER)-resident luminalproteins have a characteristic ER retrieval signal, KDEL, or its variants at their C terminus. Our previous work searching EST databases for proteins containing the C-terminal KDEL motif predicted some novel murine proteins, one of which designated JPDI (J-domaincontaining protein disulfide isomerase-like protein) is characterized in this study. The primary structure of JPDI is unique, because in addition to a J-domain motif adjacent to the N-terminal translocation signal sequence, four thioredoxin-like motifs were found in a single polypeptide. As examined by Northern blotting, the expression of JPDI was essentially ubiquitous in tissues and almost independent of ER stress. A computational prediction that JPDI is an ER-resident luminal protein was experimentally supported by immunofluorescent staining of epitope-tagged JPDI-expressing cells together with glycosylation and protease protection studies of this protein. JPDI probably acts as a DnaJlike partner of BiP, because a recombinant protein carrying the J-domain of JPDI associated with BiP in an ATP-dependent manner and enhanced its ATPase activity. We speculate that for the folding of some proteins in the ER, chaperoning by BiP and formation of proper disulfide bonds may synchronously occur in a JPDI-dependent manner.

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Protein disulfide isomerases exploit synergy between catalytic and specific binding domains

Cited by 171 publications

References 48 publications

ERp57 Is a Multifunctional Thiol-Disulfide Oxidoreductase

ERp57 Is a Multifunctional Thiol-Disulfide Oxidoreductase

Saccharomyces cerevisiaeRot1 Is an Essential Molecular Chaperone in the Endoplasmic Reticulum

JPDI, a Novel Endoplasmic Reticulum-resident Protein Containing Both a BiP-interacting J-domain and Thioredoxin-like Motifs

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