The oxidoreductase ERp57 efficiently reduces partially folded in preference to fully folded MHC class I molecules

Antony N Antoniou, Stuart Ford, Magnus Alphey, Andrew Osborne, Tim Elliott, Simon J Powis

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2655-2663
Number of pages9
JournalEMBO Journal
Volume21
Issue number11
DOIs
Publication statusPublished - 3 Jun 2002
Externally publishedYes

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