Redox-regulated export of the major histocompatibility complex class I-peptide complexes from the endoplasmic reticulum.
In contrast to the fairly well-characterized mechanism of assembly of MHC class I-peptide complexes, the disassembly mechanism by which peptide-loaded MHC class I molecules are released from the peptide-loading complex and exit the endoplasmic reticulum (ER) is poorly understood. Optimal peptide binding by MHC class I molecules is assumed to be sufficient for triggering exit of peptide-filled MHC class I molecules from the ER. We now show that protein disulfide isomerase (PDI) controls MHC class I disassembly by regulating dissociation of the tapasin-ERp57 disulfide conjugate. PDI acts as a peptide-dependent molecular switch; in the peptide-bound state, it binds to tapasin and ERp57 and induces dissociation of the tapasin-ERp57 conjugate. In the peptide-free state, PDI is incompetent to bind to tapasin or ERp57 and fails to dissociate the tapasin-ERp57 conjugates, resulting in ER retention of MHC class I molecules. Thus, our results indicate that even after optimal peptide loading, MHC class I disassembly does not occur by default but, rather, is a regulated process involving PDI-mediated interactions within the peptide-loading complex.
Lee
Sungwook
S
National Creative Research Center for Antigen Presentation, Department of Biological Sciences, Seoul National University, Seoul 151-747, Korea.
Park
Boyoun
B
Kang
Kwonyoon
K
Ahn
Kwangseog
K
D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D021381:Protein Transport
D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human