title: ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly.
abstract: The assembly of newly synthesized MHC class I molecules within the endoplasmic reticulum and their association with the transporter associated with antigen processing (TAP) is a process involving the chaperones calnexin and calreticulin. Using peptide mapping by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to identify a new component, we now introduce a third molecular chaperone, the thiol-dependent reductase ER-60 (ERp57/GRP58/ERp61/HIP-70/Q2), into this process. ER-60 is found in MHC class I heavy chain complexes with calnexin that are generated early during the MHC class I assembly pathway. The thiol reductase activity of ER-60 raises the possibility that ER-60 is involved in the disulfide bond formation within heavy chains. In addition, ER-60 is part of the late assembly complexes consisting of MHC class I, tapasin, TAP, calreticulin and calnexin. In a beta2-microglobulin (beta2m)-negative mouse cell line, S3, ER-60-calnexin-heavy chain complexes are shown to bind to TAP, suggesting that beta2m is not required for the association of MHC class I heavy chains with TAP.
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center, In Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: J A
authors.initials: JA
authors.lastname: Lindquist
authors.forename: O N
authors.initials: ON
authors.lastname: Jensen
authors.forename: M
authors.initials: M
authors.lastname: Mann
authors.forename: G J
authors.initials: GJ
authors.lastname: Hämmerling
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin; D037282:Calreticulin; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D007212:Indolizines / Q000494:pharmacology; D007535:Isomerases / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011490:Protein Disulfide Reductase (Glutathione) / Q000737:chemistry / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases; D011817:Rabbits; D012261:Ribonucleoproteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D000520:alpha-Glucosidases; D001613:beta 2-Microglobulin / Q000378:metabolism; D054836:Indolizidines
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D017920:Antiporters; D002135:Calcium-Binding Proteins; D037281:Calnexin; D037282:Calreticulin; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D007212:Indolizines; D007535:Isomerases; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D011490:Protein Disulfide Reductase (Glutathione); D019704:Protein Disulfide-Isomerases; D012261:Ribonucleoproteins; D000520:alpha-Glucosidases; D001613:beta 2-Microglobulin; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; C107762:tapasin; C071692:TAP2 protein, human; C042059:glucosidase I; C513195:Pdia3 protein, mouse; C085868:PDIA3 protein, human; C037806:castanospermine; D054836:Indolizidines