1. Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90.
- Author
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Schmauder L, Absmeier E, Bepperling A, Barkovits K, Marcus K, and Richter K
- Subjects
- Animals, Caenorhabditis elegans chemistry, Caenorhabditis elegans Proteins chemistry, Cell Cycle Proteins chemistry, HSP40 Heat-Shock Proteins chemistry, HSP90 Heat-Shock Proteins chemistry, Models, Molecular, Protein Binding, Protein Folding, Protein Interaction Maps, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins metabolism, Cell Cycle Proteins metabolism, HSP40 Heat-Shock Proteins metabolism, HSP90 Heat-Shock Proteins metabolism
- Abstract
The molecular chaperones Hsc70 and Hsp90 are required for proteostasis control and specific folding of client proteins in eukaryotic and prokaryotic organisms. Especially in eukaryotes these ATP-driven molecular chaperones are interacting with cofactors that specify the client spectrum and coordinate the ATPase cycles. Here we find that a Hsc70-cofactor of the Hsp40 family from nematodes, DNJ-13, directly interacts with the kinase-specific Hsp90-cofactor CDC-37. The interaction is specific for DNJ-13, while DNJ-12 another DnaJ-like protein of C. elegans, does not bind to CDC-37 in a similar manner. Analytical ultracentrifugation is employed to show that one CDC-37 molecule binds to a dimeric DNJ-13 protein with low micromolar affinity. We perform cross-linking studies with mass spectrometry to identify the interaction site and obtain specific cross-links connecting the N-terminal J-domain of DNJ-13 with the N-terminal domain of CDC-37. Further AUC experiments reveal that both, the N-terminal part of CDC-37 and the C-terminal domain of CDC-37, are required for efficient interaction. Furthermore, the presence of DNJ-13 strengthens the complex formation between CDC-37 and HSP-90 and modulates the nucleotide-dependent effects. These findings on the interaction between Hsp40 proteins and Hsp90-cofactors provide evidence for a more intricate interaction between the two chaperone systems during client processing., (© 2021. The Author(s).)
- Published
- 2021
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