ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase.

Mazzarella, Richard; Srinivasan, Mythili; Haugejorden, S. M.; Green, M.

doi:10.1016/s0021-9258(19)40163-4

Cited by 244 publications

(18 citation statements)

References 22 publications

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“…There are recognizable a, a′ and b sequences in the ERp60 and ERp72 homologues of PDI [20,21], suggesting that they arose from the same ancestor as PDI; in the case of ERp72, a further gene-shuffling event has added another thioredoxin-like module to the amino terminus [21]. Thus, PDI demonstrates that modular proteins arose in the distant past, in contrast to the common belief that such modular evolution is a recent phenomenon.…”

Section: Modular Structure Of Pdimentioning

confidence: 99%

The folding catalyst protein disulfide isomerase is constructed of active and inactive thioredoxin modules

et al. 1997

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Our determination of the global fold of the b domain of PDI by NMR reveals that, like the a domain, the b domain contains the thioredoxin motif, even though the b domain has no significant amino-acid sequence similarities to any members of the thioredoxin family. This observation, together with indications that the b' domain adopts a similar fold, suggests that PDI consists of active and inactive thioredoxin modules. These modules may have been adapted during evolution to provide PDI with its complete spectrum of enzymatic activities.

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Section: Modular Structure Of Pdimentioning

confidence: 99%

The folding catalyst protein disulfide isomerase is constructed of active and inactive thioredoxin modules

et al. 1997

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“…Further, appending this KDEL sequence to a secretory protein resulted in a failure of secretion and protein accumulation within the ER ( Munro and Pelham, 1987 ). Subsequent studies identified KEEL, RDEL, and QEDL as putative ERS ( Fliegel et al, 1990 ; Mazzarella et al, 1990 ; Mazzarella et al, 1994 ). A bioinformatic approach intended to identify ER localization motifs found 46 putative ERS even while using a data set restricted to human proteins with the terminal four amino acids XX (DE)(FLM) ( Raykhel et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Computational Modeling of C-Terminal Tails to Predict the Calcium-Dependent Secretion of Endoplasmic Reticulum Resident Proteins

Xie

Verma

et al. 2021

Front. Chem.

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The lumen of the endoplasmic reticulum (ER) has resident proteins that are critical to perform the various tasks of the ER such as protein maturation and lipid metabolism. These ER resident proteins typically have a carboxy-terminal ER retention/retrieval sequence (ERS). The canonical ERS that promotes ER retrieval is Lys-Asp-Glu-Leu (KDEL) and when an ER resident protein moves from the ER to the Golgi, KDEL receptors (KDELRs) in the Golgi recognize the ERS and return the protein to the ER lumen. Depletion of ER calcium leads to the mass departure of ER resident proteins in a process termed exodosis, which is regulated by KDELRs. Here, by combining computational prediction with machine learning-based models and experimental validation, we identify carboxy tail sequences of ER resident proteins divergent from the canonical “KDEL” ERS. Using molecular modeling and simulations, we demonstrated that two representative non-canonical ERS can stably bind to the KDELR. Collectively, we developed a method to predict whether a carboxy-terminal sequence acts as a putative ERS that would undergo secretion in response to ER calcium depletion and interacts with the KDELRs. The interaction between the ERS and the KDELR extends beyond the final four carboxy terminal residues of the ERS. Identification of proteins that undergo exodosis will further our understanding of changes in ER proteostasis under physiological and pathological conditions where ER calcium is depleted.

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“…The domain organization varies between the different PDIs. For instance, the stress-induced protein ERp72 has three active thioredoxin-like proteins, as compared with the two of Pdi1p (Dorner et al, 1990;Mazzarella et al, 1990). ERp72 and other genes encoding mammalian PDIs are able to suppress the lethal effects of deletion of PDI1 in yeast (Günther et al, 1993;Laboissière et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Functional Differences in Yeast Protein Disulfide Isomerases

Nørgaard

Westphal

Tachibana

et al. 2001

The Journal of Cell Biology

115

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PDI1 is the essential gene encoding protein disulfide isomerase in yeast. The Saccharomyces cerevisiae genome, however, contains four other nonessential genes with homology to PDI1: MPD1, MPD2, EUG1, and EPS1. We have investigated the effects of simultaneous deletions of these genes. In several cases, we found that the ability of the PDI1 homologues to restore viability to a pdi1-deleted strain when overexpressed was dependent on the presence of low endogenous levels of one or more of the other homologues. This shows that the homologues are not functionally interchangeable. In fact, Mpd1p was the only homologue capable of carrying out all the essential functions of Pdi1p. Furthermore, the presence of endogenous homologues with a CXXC motif in the thioredoxin-like domain is required for suppression of a pdi1 deletion by EUG1 (which contains two CXXS active site motifs). This underlines the essentiality of protein disulfide isomerase-catalyzed oxidation. Most mutant combinations show defects in carboxypeptidase Y folding as well as in glycan modification. There are, however, no significant effects on ER-associated protein degradation in the various protein disulfide isomerase-deleted strains.

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ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase.

Cited by 244 publications

References 22 publications

The folding catalyst protein disulfide isomerase is constructed of active and inactive thioredoxin modules

The folding catalyst protein disulfide isomerase is constructed of active and inactive thioredoxin modules

Computational Modeling of C-Terminal Tails to Predict the Calcium-Dependent Secretion of Endoplasmic Reticulum Resident Proteins

Functional Differences in Yeast Protein Disulfide Isomerases

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