title: The group II chaperonin TRiC protects proteolytic intermediates from degradation in the MHC class I antigen processing pathway.
abstract: MHC class I molecules present precisely cleaved peptides of intracellular proteins on the cell surface. For most antigenic precursors, presentation requires transport of peptide fragments into the ER, but the nature of the cytoplasmic peptides and their chaperones is obscure. By tracking proteolytic intermediates in living cells, we show that intracellular proteolysis yields a mixture of antigenic peptides containing only N-terminal flanking residues for ER transport. Some of these peptides were bound to the group II chaperonin TRiC and were protected from degradation. Destabilization of TRiC by RNA interference inhibited the expression of peptide-loaded MHC I molecules on the cell surface. Thus, the TRiC chaperonin serves a function in protecting proteolytic intermediates in the MHC I antigen processing pathway.
authors.affiliation: Division of Immunology, Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA 94720, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000378:metabolism*; D019556:COS Cells; D002470:Cell Survival / Q000276:immunology; D018833:Chaperonins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003599:Cytoskeleton / Q000276:immunology; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D005057:Eukaryotic Cells / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D017434:Protein Structure, Tertiary / Q000502:physiology; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D010446:Peptide Fragments; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D018833:Chaperonins