A role for the thiol-dependent reductase ERp57 in the assembly of MHC class I molecules.
An important mammalian defence strategy against intracellular pathogens is the presentation of cytoplasmically derived short peptides by major histocompatibility complex (MHC) class I molecules to cytotoxic T lymphocytes. MHC class I molecules assemble in the endoplasmic reticulum (ER) with chaperones, including calnexin and calreticulin, before binding to the transporter associated with antigen processing (TAP). We show here that the thiol-dependent reductase ERp57 (also known as ER60 protease) is involved in MHC class I assembly. ERp57 co-purified with the rat TAP complex (comprising TAP1 and TAP2), and associated with MHC class I molecules at an early stage in their biosynthesis. This association was sensitive to castanospermine, which inhibits the processing of glycoproteins. Human MHC class I molecules were also found to associate with ERp57. We conclude that ERp57 is a newly identified component of the MHC class I pathway, and that it appears to interact with MHC class I molecules before they associate with TAP.
Morrice
N A
NA
MRC Protein Phosphorylation Unit, University of Dundee, Scotland.
Powis
S J
SJ
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007535:Isomerases / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D011490:Protein Disulfide Reductase (Glutathione) / Q000378:metabolism / Q000502:physiology*; D019704:Protein Disulfide-Isomerases; D051381:Rats; D014407:Tumor Cells, Cultured
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C486172:Tap1 protein, rat; C489514:Tap2 protein, rat; C071692:TAP2 protein, human; D011490:Protein Disulfide Reductase (Glutathione); D007535:Isomerases; C513196:PDIA3 protein, rat; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human