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PMID: 15525676 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

ERdj3, a stress-inducible endoplasmic reticulum DnaJ homologue, serves as a cofactor for BiP's interactions with unfolded substrates.

Molecular biology of the cell ·Vol. 16 ·No. 1 ·2005-01-00 ·Pages 40-50

Shen Y, Hendershot LM

Abstract

We recently identified ERdj3 as a component of unassembled immunoglobulin (Ig) heavy chain:BiP complexes. ERdj3 also associates with a number of other protein substrates, including unfolded light chains, a nonsecreted Ig light chain mutant, and the VSV-G ts045 mutant at the nonpermissive temperature. We produced an ERdj3 mutant that was unable to stimulate BiP's ATPase activity in vitro or to bind BiP in vivo. This mutant retained the ability to interact with unfolded protein substrates, suggesting that ERdj3 binds directly to proteins instead of via interactions with BiP. BiP remained bound to unfolded light chains longer than ERdj3, which interacted with unfolded light chains initially, but quickly disassociated before protein folding was completed. This suggests that ERdj3 may bind first to substrates and serve to inhibit protein aggregation until BiP joins the complex, whereas BiP remains bound until folding is complete. Moreover, our findings support a model where interactions with BiP help trigger the release of ERdj3 from the substrate:BiP complex.

MeSH Terms
Adenosine Triphosphatases/metabolism Amino Acid Motifs Animals Blotting, Northern COS Cells Cell Line, Tumor DNA/metabolism DNA, Complementary/metabolism Endopeptidase K/pharmacology Endoplasmic Reticulum Chaperone BiP Glycoside Hydrolases/metabolism HSP40 Heat-Shock Proteins HeLa Cells Heat-Shock Proteins/chemistry,metabolism Humans Immunoprecipitation Microsomes/metabolism Molecular Chaperones/chemistry,metabolism,physiology Mutation Protein Binding Protein Biosynthesis Protein Folding Protein Sorting Signals Recombinant Proteins/chemistry Temperature Time Factors Transfection Tunicamycin/pharmacology Up-Regulation
Chemicals
DNA, Complementary DNAJB11 protein, human Endoplasmic Reticulum Chaperone BiP HSP40 Heat-Shock Proteins Heat-Shock Proteins Molecular Chaperones Protein Sorting Signals Recombinant Proteins Tunicamycin DNA Glycoside Hydrolases Endopeptidase K Adenosine Triphosphatases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Shen Ying
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hendershot Linda M
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e04-05-0434
Published
2005-01-00
Epub
2004-00-03
Pages
40-50
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC539150
Subset
IM
Grants
NCI NIH HHS · P30 CA021765 · United States
NIGMS NIH HHS · R01 GM054068 · United States
NCI NIH HHS · CA21765 · United States
NIGMS NIH HHS · GM-54068 · United States
External Links
PubMed source DOI: 10.1091/mbc.e04-05-0434 PMC Full Text View journal details
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