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PMID: 9545232 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly.

The EMBO journal ·Vol. 17 ·No. 8 ·1998-04-15 ·Pages 2186-95

Lindquist JA, Jensen ON, Mann M, Hämmerling GJ

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.

MeSH Terms
ATP Binding Cassette Transporter, Subfamily B, Member 2 ATP Binding Cassette Transporter, Subfamily B, Member 3 ATP-Binding Cassette Transporters/metabolism Amino Acid Sequence Animals Antiporters/genetics,metabolism Calcium-Binding Proteins/metabolism Calnexin Calreticulin Cell Line Enzyme Inhibitors/pharmacology Glycoside Hydrolase Inhibitors Heat-Shock Proteins/chemistry,metabolism Histocompatibility Antigens Class I/metabolism Humans Immunoglobulins/genetics,metabolism Indolizines/pharmacology Isomerases/chemistry,metabolism Membrane Transport Proteins Mice Molecular Chaperones/chemistry,metabolism Molecular Sequence Data Precipitin Tests Protein Disulfide Reductase (Glutathione)/chemistry,metabolism Protein Disulfide-Isomerases Rabbits Ribonucleoproteins/metabolism Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Tumor Cells, Cultured alpha-Glucosidases beta 2-Microglobulin/metabolism
Chemicals
ATP Binding Cassette Transporter, Subfamily B, Member 2 ATP Binding Cassette Transporter, Subfamily B, Member 3 ATP-Binding Cassette Transporters Antiporters Calcium-Binding Proteins Calreticulin Enzyme Inhibitors Glycoside Hydrolase Inhibitors Heat-Shock Proteins Histocompatibility Antigens Class I Immunoglobulins Indolizines Membrane Transport Proteins Molecular Chaperones Ribonucleoproteins TAP1 protein, human Tap1 protein, mouse Tap2 protein, mouse beta 2-Microglobulin tapasin Calnexin TAP2 protein, human Protein Disulfide Reductase (Glutathione) glucosidase I alpha-Glucosidases Isomerases Pdia3 protein, mouse Protein Disulfide-Isomerases PDIA3 protein, human castanospermine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lindquist J A
Department of Molecular Immunology, German Cancer Research Center, In Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Jensen O N
Mann M
Hämmerling G J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.8.2186
Published
1998-04-15
Pages
2186-95
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170563
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/17.8.2186 PMC Full Text View journal details
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