J domain co-chaperone specificity defines the role of BiP during protein translocation

Shruthi S. Vembar, Martin C. Jonikas, Linda M. Hendershot, Jonathan S. Weissman, Jeffrey L. Brodsky

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Hsp70 chaperones can potentially interact with one of several J domain-containing Hsp40 co-chaperones to regulate distinct cellular processes. However, features within Hsp70s that determine Hsp40 specificity are undefined. To investigate this question, we introduced mutations into the ER-lumenal Hsp70, BiP/ Kar2p, and found that an R217A substitution in the J domain-interacting surface of BiP compromised the physical and functional interaction with Sec63p, an Hsp40 required for ER translocation. In contrast, interaction with Jem1p, an Hsp40 required for ER-associated degradation, was unaffected. Moreover, yeast expressing R217A BiP exhibited defects in translocation but not in ER-associated degradation. Finally, the genetic interactions of the R217A BiP mutant were found to correlate with those of known translocation mutants. Together, our results indicate that residues within the Hsp70 J domain-interacting surface help confer Hsp40 specificity, in turn influencing distinct chaperone-mediated cellular activities.

Original languageEnglish (US)
Pages (from-to)22484-22494
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number29
DOIs
StatePublished - Jul 16 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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