title: The oxidoreductase ERp57 efficiently reduces partially folded in preference to fully folded MHC class I molecules.
abstract: The oxidoreductase ERp57 is an integral component of the peptide loading complex of major histocompatibility complex (MHC) class I molecules, formed during their chaperone-assisted assembly in the endoplasmic reticulum. Misfolded MHC class I molecules or those denied suitable peptides are retrotranslocated and degraded in the cytosol. The presence of ERp57 during class I assembly suggests it may be involved in the reduction of intrachain disulfides prior to retrotranslocation. We have studied the ability of ERp57 to reduce MHC class I molecules in vitro. Recombinant ERp57 specifically reduced partially folded MHC class I molecules, whereas it had little or no effect on folded and peptide-loaded MHC class I molecules. Reductase activity was associated with cysteines at positions 56 and 405 of ERp57, the N-terminal residues of the active CXXC motifs. Our data suggest that the reductase activity of ERp57 may be involved during the unfolding of MHC class I molecules, leading to targeting for degradation.
authors.affiliation: Division of Cell Biology and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
authors.forename: Antony N
authors.initials: AN
authors.lastname: Antoniou
authors.forename: Stuart
authors.initials: S
authors.lastname: Ford
authors.forename: Magnus
authors.initials: M
authors.lastname: Alphey
authors.forename: Andrew
authors.initials: A
authors.lastname: Osborne
authors.forename: Tim
authors.initials: T
authors.lastname: Elliott
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Powis
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry*; D018076:DNA, Complementary / Q000378:metabolism; D004220:Disulfides; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007535:Isomerases / Q000737:chemistry* / Q000378:metabolism*; D008285:Major Histocompatibility Complex; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D011233:Precipitin Tests; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases; D017510:Protein Folding; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
chemical_list: D018076:DNA, Complementary; D004220:Disulfides; D006360:Heat-Shock Proteins; D007328:Insulin; D010455:Peptides; D011994:Recombinant Proteins; D007535:Isomerases; C513196:PDIA3 protein, rat; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human; D003545:Cysteine