The redox activity of ERp57 is not essential for its functions in MHC class I peptide loading.
ERp57 is an oxidoreductase that, in conjunction with calnexin and calreticulin, assists disulfide bond formation in folding glycoproteins. ERp57 also forms a mixed disulfide with the MHC class I-specific chaperone tapasin, and this dimeric conjugate edits the peptide repertoire bound by MHC class I molecules. In cells unable to form the conjugate, because of tapasin mutation in human studies or ERp57 deletion in mouse studies, peptide loading is impeded. Subtle differences between the mouse and human systems have been observed. Here, we address these differences and expand the analysis to investigate the role of ERp57 redox functions in MHC class I peptide loading. We show in human cells that in the absence of conjugate formation MHC class I recruitment and/or stabilization in the MHC class I peptide-loading complex is impaired, similar to observations in mouse cells. However, we found no role for the enzymatic activities of either the a or a' domain redox sites of ERp57 in peptide loading. Our data argue that the function of ERp57 in peptide loading is likely caused by other ERp57 functional domains or a combinatorial feature of the tapasin-ERp57 conjugate.
Peaper
David R
DR
Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8011, USA.
Cresswell
Peter
P
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001665:Binding Sites; D005805:Genes, MHC Class I; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D019704:Protein Disulfide-Isomerases / Q000235:genetics* / Q000502:physiology*; D017434:Protein Structure, Tertiary
D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin; D010088:Oxidoreductases; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human