A role for protein disulfide isomerase in the early folding and assembly of MHC class I molecules.
Proper folding and assembly of major histocompatibility complex (MHC) class I complexes are essential for optimal peptide loading and subsequent antigen presentation. MHC class I folding involves the coordinated formation of multiple disulfide bonds within MHC class I molecules. However, the regulation of disulfide bond formation during the early process of MHC class I folding is uncharacterized. Here, we show that protein disulfide isomerase (PDI) catalyzes the disulfide bond formation of MHC class I molecules and thereby facilitates the assembly of MHC class I heavy chain with beta(2)-microglobulin (beta(2)m). Depletion of PDI but not ERp57 by RNAi interfered with the disulfide bond formation in the MHC class I molecules. In the absence of PDI, the association of free class I heavy chain with calnexin increased, whereas the assembly of MHC class I heavy chain-beta(2)m heterodimers was delayed. These observations suggest that PDI-catalyzed disulfide bond formation of MHC class I molecules is an event downstream of the interaction of class I molecules with calnexin and upstream of their interaction with beta(2)m. Thus, our data establish a critical function for PDI in the early assembly of MHC class I molecules.
Kang
Kwonyoon
K
National Creative Research Center for Antigen Presentation, Department of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.
Park
Boyoun
B
Oh
Changhoon
C
Cho
Kwangmin
K
Ahn
Kwangseog
K
D000818:Animals; D002460:Cell Line; D004220:Disulfides / Q000737:chemistry; D005805:Genes, MHC Class I; D006367:HeLa Cells; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D008954:Models, Biological; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D004220:Disulfides; D001613:beta 2-Microglobulin; D019704:Protein Disulfide-Isomerases