Efficient dissociation of the p88 chaperone from major histocompatibility complex class I molecules requires both beta 2-microglobulin and peptide.
Previously, we showed that an 88-kD protein (p88) associates rapidly and quantitatively with newly synthesized murine major histocompatibility complex class I molecules within the endoplasmic reticulum (ER). This interaction is transient and dissociation of p88 appears to be rate limiting for transport of class I molecules from the ER to the Golgi apparatus. In this report, we examine the relationship between p88 interaction and assembly of the ternary complex of class I heavy chain beta 2-microglobulin (beta 2m), and peptide ligand. In both murine and human beta 2m-deficient cells, in which little or no transport of class I heavy chains is observed, p88 remained associated with intracellular heavy chains throughout their lifetime. In murine RMA-S cells, which are apparently defective in accumulating peptide ligands for class I within the ER, prolonged association of p88 with "empty" heavy chain-beta 2m heterodimers was also observed. However, p88 dissociated slowly in parallel with the slow rate of ER to Golgi transport of empty class I molecules in these cells. The close correlation between p88 association and impaired class I transport suggests that p88 functions to retain incompletely assembled class I molecules in the ER. We propose that conformational changes in class I heavy chains induced by the binding of both beta 2m and peptide are required for efficient p88 dissociation and subsequent class I transport.
Degen
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E
Department of Biochemistry, University of Toronto, Ontario, Canada.
Cohen-Doyle
M F
MF
Williams
D B
DB
D000951:Antigens, Neoplasm / Q000302:isolation & purification / Q000378:metabolism*; D002051:Burkitt Lymphoma; D002478:Cells, Cultured; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D016399:Lymphoma, T-Cell; D046911:Macromolecular Substances; D008297:Male; D008970:Molecular Weight; D014162:Transfection; D001613:beta 2-Microglobulin / Q000378:metabolism*
D000951:Antigens, Neoplasm; D003432:Cross-Linking Reagents; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D001613:beta 2-Microglobulin