Structure of the Noncatalytic Domains and Global Fold of the Protein Disulfide Isomerase ERp72

Kozlov, Guennadi; Määttänen, Pekka; Schrag, Joseph D.; Hura, Greg L.; Gabrielli, Lisa; Cygler, Mirosław; Thomas, David Y.; Gehring, Kalle

doi:10.1016/j.str.2009.02.016

Cited by 44 publications

(49 citation statements)

References 58 publications

(77 reference statements)

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“…ERp27 possesses a substrate-binding site very similar to that found in human PDI (43), yeast PDI (44), and ERp44 (45) which, however, is blocked by a network of salt bridges in ERp57 (46) and ERp72 (47). It is therefore highly likely that both PDI and ERp44 also possess the ability to distinguish between the folded and unfolded state of potential substrates as has been demonstrated for ERp27.…”

Section: Discussionmentioning

confidence: 84%

The Crystal Structure of the Protein-Disulfide Isomerase Family Member ERp27 Provides Insights into Its Substrate Binding Capabilities

Kober¹,

Koelmel²,

Kuper

et al. 2013

Journal of Biological Chemistry

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Background: ERp27 is a redox-inactive member of the protein-disulfide isomerase family. Results: The crystal structure of ERp27 reveals how the substrate-binding site can be modulated by conformational changes. Conclusion: ERp27 is induced during ER stress and binds misfolded proteins. Significance: ERp27 may act as a safety overflow under stress conditions, funneling excess misfolded protein onto ERp57.

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Section: Discussionmentioning

confidence: 84%

The Crystal Structure of the Protein-Disulfide Isomerase Family Member ERp27 Provides Insights into Its Substrate Binding Capabilities

Kober¹,

Koelmel²,

Kuper

et al. 2013

Journal of Biological Chemistry

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“…The main substrates that formed mixed disulphides with this enzyme following in vitro translation were glycoproteins, which were particularly apparent when the interaction with calnexin was blocked. A recent structural analysis of the bbЈ domain of ERp72 shows strong similarity to ERp57, although ERp72 does not interact with calnexin (Kozlov et al, 2009). It might be that when substrates that are normally acted upon by ERp57 are prevented from entering the calnexin cycle they can then become substrates for ERp72.…”

Section: Discussionmentioning

confidence: 99%

Protein disulphide isomerase family members show distinct substrate specificity: P5 is targeted to BiP client proteins

Jessop

Watkins

Simmons

et al. 2009

Journal of Cell Science

176

210

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At least 17 members of the protein disulphide isomerase (PDI) family of oxidoreductases are present in the endoplasmic reticulum (ER) of mammalian cells. They are thought to catalyse disulphide formation to aid folding or to regulate protein function; however, little is known about their individual functions. Here, we show that some proteins that enter the ER are clients for single oxidoreductases, whereas others are clients for several PDI-like enzymes. We previously identified potential substrates for ERp57, and here identify substrates for ERp18 and ERp46. In addition, we analysed the specificity of substrates towards PDI, ERp72, ERp57, ERp46, ERp18 and P5. Strikingly, ERp18 shows specificity towards a component of the complement cascade, pentraxin-related protein PTX3, whereas ERp46 has specificity towards peroxiredoxin-4, a thioredoxin peroxidase. By contrast, most PDI family members react with Ero1. Moreover, P5 forms a non-covalent complex with immunoglobulin heavy chain binding protein (BiP) and shows specificity towards BiP client proteins. These findings highlight cooperation between BiP and P5, and demonstrate that individual PDI family members recognise specific substrate proteins. Supplementary material available online at

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“…2b). Previously, this tryptophan was suggested to be involved in the binding to substrate proteins based on its proximity to the catalytic cysteines (Kozlov et al, 2009). In the structure of the PDI-family member ERp57 in complex with tapasin, the residue at the position of Trp349 makes important intermolecular contacts with tapasin (Dong et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

Structure of the third catalytic domain of the protein disulfide isomerase ERp46

et al. 2012

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PDB Reference: third catalytic domain of ERp46, 3uvt.Protein disulfide isomerases are responsible for catalyzing the proper oxidation and isomerization of disulfide bonds of newly synthesized proteins in the endoplasmic reticulum. Here, the crystal structure of the third catalytic domain of protein disulfide isomerase ERp46 (also known as protein disulfide isomerase A5 and TXNDC5) was determined to 2.0 Å resolution. The structure shows a typical thioredoxin-like fold, but also identifies regions of high structural variability. In particular, the loop between helix 2 and strand 3 adopts strikingly different conformations among the five chains of the asymmetric unit. Cys381 and Cys388 form a structural disulfide and its absence in one of the molecules leads to dramatic conformational changes. The tryptophan residue Trp349 of this molecule inserts into the cavity formed by helices 1 and 3 of a neighbouring molecule, potentially mimicking the interactions of ERp46 with misfolded substrates.

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Structure of the Noncatalytic Domains and Global Fold of the Protein Disulfide Isomerase ERp72

Cited by 44 publications

References 58 publications

The Crystal Structure of the Protein-Disulfide Isomerase Family Member ERp27 Provides Insights into Its Substrate Binding Capabilities

The Crystal Structure of the Protein-Disulfide Isomerase Family Member ERp27 Provides Insights into Its Substrate Binding Capabilities

Protein disulphide isomerase family members show distinct substrate specificity: P5 is targeted to BiP client proteins

Structure of the third catalytic domain of the protein disulfide isomerase ERp46

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