The Thiol-dependent Reductase ERp57 Interacts Specifically with N-Glycosylated Integral Membrane Proteins

Elliott, John G.; Oliver, Jason D.; High, Stephen

doi:10.1074/jbc.272.21.13849

Cited by 124 publications

(103 citation statements)

References 46 publications

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“…Ferrari and H.-D. So$ ling, unpublished work), and although ERp72, ERp57, PDIp and ERp28 have been reported to interact with peptides and\or malfolded proteins [10,[102][103][104][105][106][107][108], only for PDIp has the interaction been indicated to be direct [108].…”

Section: Peptide Bindingmentioning

confidence: 97%

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The protein disulphide-isomerase family: unravelling a string of folds

Ferrari

Söling

1999

Biochemical Journal

406

359

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The mammalian protein disulphide-isomerase (PDI) family encompasses several highly divergent proteins that are involved in the processing and maturation of secretory proteins in the endoplasmic reticulum. These proteins are characterized by the presence of one or more domains of roughly 95-110 amino acids related to the cytoplasmic protein thioredoxin. All but the PDI-D subfamily are composed entirely of repeats of such domains, with at least one domain containing and one domain lacking a redox-active -Cys-Xaa-Xaa-Cys-tetrapeptide. In addition to their known roles as redox catalysts and isomerases, the last few years have revealed additional functions of the PDI proteins,

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Section: Peptide Bindingmentioning

confidence: 97%

“…Redox-active-site [60,144] pendent manner [104,105], but probably only indirectly via interactions with calnexin or calsequestrin [106,107], as ERp57 itself lacks lectin-like properties [106]. This is in contrast with PDI, which interacts with proteins independently of their glycosylation status [65,104,107].…”

Section: Molecularmentioning

confidence: 99%

The protein disulphide-isomerase family: unravelling a string of folds

Ferrari

Söling

1999

Biochemical Journal

406

359

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“…ERp57 has thiol-dependent reductase activity (29), cysteine-dependent protease activity (30,31), and is known to interact with glycoproteins in a manner that can involve forming complexes with either CXN and CRT (32)(33)(34). Three recent reports demonstrated that ERp57 is detected in association with class I molecules before peptide binding (26 -28).…”

Section: Association Of Erp57 Withmentioning

confidence: 99%

Association of ERp57 with Mouse MHC Class I Molecules Is Tapasin Dependent and Mimics That of Calreticulin and not Calnexin

Harris

Lybarger

et al. 2001

The Journal of Immunology

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Before peptide binding in the endoplasmic reticulum, the class I heavy (H) chain-β2-microglobulin complexes are detected in association with TAP and two chaperones, TPN and CRT. Recent studies have shown that the thiol-dependent reductase, ERp57, is also present in this peptide-loading complex. However, it remains controversial whether the association of ERp57 with MHC class I molecules precedes their combined association with the peptide-loading complex or whether ERp57 only associates with class I molecules in the presence of TPN. Resolution of this controversy could help determine the role of ERp57 in class I folding and/or assembly. To define the mouse class I H chain structures involved in interaction with ERp57, we tested chaperone association of Ld mutations at residues 134 and 227/229 (previously implicated in TAP association), residues 86/88 (which ablate an N-linked glycan), and residue 101 (which disrupts a disulfide bond). The association of ERp57 with each of these mutant H chains showed a complete concordance with CRT, TAP, and TPN but not with calnexin. Furthermore, ERp57 failed to associate with H chain in TPN-deficient .220 cells. These combined data demonstrate that, during the assembly of the peptide-loading complex, the association of ERp57 with mouse class I is TPN dependent and parallels that of CRT and not calnexin.

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“…By applying chemical cross-linking techniques, it was demonstrated that in canine pancreatic microsomes, ERp57 associates only with glycosylated versions of membrane and secretory proteins [13,14]. This interaction depends upon glucose trimming and is transient [13], similar to the binding of calnexin and calreticulin.…”

mentioning

confidence: 99%

The transient association of ERp57 with N‐glycosylated proteins is regulated by glucose trimming

Wal

Oliver

High

1998

European Journal of Biochemistry

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The thiol-dependent reductase ERp57 has been shown to interact specifically with in vitro synthesised glycoproteins imported into canine pancreatic microsomes. On this basis, it was proposed that ERp57 forms part of a glycoprotein-specific folding 'machinery', present in the lumen of the endoplasmic reticulum (ER). In this study, we have investigated the interaction of ERp57 with newly synthesised proteins using semi-permeabilised mammalian cells (SP cells), in which the ER remains essentially intact and, hence, resembles that of a living cell. We demonstrate that ERp57 interacts preferentially with the glycosylated versions of soluble and membrane proteins, and that this interaction occurs in combination with calnexin and calreticulin. For the first time, we have performed a detailed analysis of the kinetics of ERp57 binding to newly synthesised glycoproteins. We find that ERp57 associates transiently with glycoproteins Ϫ a characteristic of molecular chaperones. Using mutant SP cells deficient in glucosidase I, we confirm that the binding of ERp57 to glycoproteins depends upon glucose trimming. We also demonstrate, for the first time, that the release of ERp57 from glycoprotein substrates is dependent upon glucose trimming. These data are combined to present a unified model for the role of ERp57/ER lectin complexes during glycoprotein folding in vivo.Keywords : endoplasmic reticulum ; ERp57/GRP58 ; molecular chaperone ; N-linked glycosylation; protein disulphide isomerase.The endoplasmic reticulum (ER) membrane is a primary site of protein synthesis in mammalian cells. Newly synthesised proteins are inserted into, or translocated across, the ER membrane, from where they can reach their final destination in one of the organelles of the secretory pathway, the plasma membrane or the cell exterior.To facilitate protein maturation, the ER is equipped with a number of membrane and soluble proteins involved in the processing, modification, folding and oligomeric assembly of newly synthesised polypeptides. ER proteins involved in protein maturation include folding enzymes, such as peptidylprolyl cisϪtrans isomerase and members of the protein disulphide isomerase (PDI) family, as well as molecular chaperones of the Hsp70 and Hsp90 class heat-shock proteins, such as immunoglobulin heavy-chain-binding protein (BiP/GRP78) and GRP94 [1].In addition to these folding enzymes and chaperones, the ER contains two proteins with lectin-like properties, namely the type-I membrane protein calnexin, and its soluble homologue, calreticulin. Calnexin and calreticulin associate transiently with a wide variety of N-glycosylated proteins, and were proposed to influence folding, oligomerisation and ER retention. Together with several enzymes that modify N-linked oligosaccharides, calnexin and calreticulin constitute an ER quality-control machinery for glycoproteins [2].Calnexin and calreticulin display a specificity for monoglucosylated oligosaccharides [2Ϫ4] that are generated in the ER by the combined actions of two A-glucosidases and a...

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The Thiol-dependent Reductase ERp57 Interacts Specifically with N-Glycosylated Integral Membrane Proteins

Cited by 124 publications

References 46 publications

The protein disulphide-isomerase family: unravelling a string of folds

The protein disulphide-isomerase family: unravelling a string of folds

Association of ERp57 with Mouse MHC Class I Molecules Is Tapasin Dependent and Mimics That of Calreticulin and not Calnexin

The transient association of ERp57 with N‐glycosylated proteins is regulated by glucose trimming

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