Participation of a novel 88-kD protein in the biogenesis of murine class I histocompatibility molecules.
Chemical cross-linking and gel permeation chromatography were used to examine early events in the biogenesis of class I histocompatibility molecules. We show that newly synthesized class I heavy chains associate rapidly and quantitatively with an 88-kD protein in three murine tumor cell lines. This protein (p88) does not appear to possess Asn-linked glycans and it is not the abundant ER protein, GRP94. The class I-p88 complex exists transiently (t1/2 = 20-45 min depending on the specific class I heavy chain) and several lines of evidence suggest that p88 dissociates from the complex while still in the ER. Dissociation is not triggered upon binding of beta 2-microglobulin to the heavy chain (t1/2 = 2-5 min). However, the rate of dissociation does correlate with the characteristic rate of ER to Golgi transport for the particular class I molecule studied. Consequently, dissociation of p88 may be rate limiting for ER to Golgi transport. Class I molecules bind antigenic peptides, apparently in the ER, for subsequent presentation to cytotoxic T lymphocytes at the cell surface. p88 could promote peptide binding or it may retain class I molecules in the ER during formation of the ternary complex of heavy chain, beta 2-microglobulin, and peptide.
Degen
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Department of Biochemistry, University of Toronto, Canada.
Williams
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DB
D000818:Animals; D002460:Cell Line; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D013388:Succinimides / Q000378:metabolism
D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D013388:Succinimides; C011240:dithiobis(succinimidylpropionate)