title: A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins.
abstract: We demonstrate the existence of a large endoplasmic reticulum (ER)-localized multiprotein complex that is comprised of the molecular chaperones BiP; GRP94; CaBP1; protein disulfide isomerase (PDI); ERdj3, a recently identified ER Hsp40 cochaperone; cyclophilin B; ERp72; GRP170; UDP-glucosyltransferase; and SDF2-L1. This complex is associated with unassembled, incompletely folded immunoglobulin heavy chains. Except for ERdj3, and to a lesser extent PDI, this complex also forms in the absence of nascent protein synthesis and is found in a variety of cell types. Cross-linking studies reveal that the majority of these chaperones are included in the complex. Our data suggest that this subset of ER chaperones forms an ER network that can bind to unfolded protein substrates instead of existing as free pools that assembled onto substrate proteins. It is noticeable that most of the components of the calnexin/calreticulin system, which include some of the most abundant chaperones inside the ER, are either not detected in this complex or only very poorly represented. This study demonstrates an organization of ER chaperones and folding enzymes that has not been previously appreciated and suggests a spatial separation of the two chaperone systems that may account for the temporal interactions observed in other studies.
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Meunier
authors.forename: Young-Kwang
authors.initials: YK
authors.lastname: Usherwood
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Chung
authors.forename: Linda M
authors.initials: LM
authors.lastname: Hendershot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D014407:Tumor Cells, Cultured
chemical_list: D037282:Calreticulin; D003432:Cross-Linking Reagents; D037281:Calnexin; D005990:Glycerol