title: Disulfide bond isomerization and the assembly of MHC class I-peptide complexes.
abstract: The presence of a disulfide bond inside the peptide binding groove of MHC class I molecules and of the thiol oxidoreductase ERp57 in the class I loading complex suggests that disulfide bond isomerization may play a role in peptide loading. Here we show that ERp57 and tapasin are disulfide linked inside the loading complex. Mutagenesis of cysteine 95 in tapasin not only abolishes formation of the ERp57-tapasin bond but also prevents complete oxidation of the class I heavy chain in the loading complex. The resulting MHC class I-beta2m heterodimers are poorly loaded with high-affinity peptides in the ER but nevertheless escape to the cell surface where they are unstable. These findings suggest a role for disulfide bond isomerization in tapasin-mediated peptide loading.
authors.affiliation: Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Tobias P
authors.initials: TP
authors.lastname: Dick
authors.forename: Naveen
authors.initials: N
authors.lastname: Bangia
authors.forename: David R
authors.initials: DR
authors.lastname: Peaper
authors.forename: Peter
authors.initials: P
authors.lastname: Cresswell
mesh_terms: D017920:Antiporters / Q000737:chemistry*; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry*; D006360:Heat-Shock Proteins / Q000737:chemistry*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D007535:Isomerases / Q000737:chemistry*; D026901:Membrane Transport Proteins; D019704:Protein Disulfide-Isomerases; D001613:beta 2-Microglobulin / Q000737:chemistry
chemical_list: D017920:Antiporters; D004220:Disulfides; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D001613:beta 2-Microglobulin; C107762:tapasin; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human; D003545:Cysteine