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

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.
Mesh Terms:
Endoplasmic Reticulum, Fungal Proteins, HSP70 Heat-Shock Proteins, Heat-Shock Proteins, Membrane Transport Proteins, Molecular Chaperones, Mutant Proteins, Mutation, Protein Processing, Post-Translational, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Transport, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Stress, Physiological, Structure-Activity Relationship, Substrate Specificity
J. Biol. Chem.
Date: Jul. 16, 2010
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