RRC ID 76054
Author Schmauder L, Absmeier E, Bepperling A, Barkovits K, Marcus K, Richter K.
Title Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90.
Journal Sci Rep
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.
Volume 11(1)
Pages 21346
Published 2021-11-1
DOI 10.1038/s41598-021-00885-4
PII 10.1038/s41598-021-00885-4
PMID 34725424
PMC PMC8560915
MeSH Animals Caenorhabditis elegans / chemistry Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / chemistry Cell Cycle Proteins / metabolism* HSP40 Heat-Shock Proteins / chemistry HSP40 Heat-Shock Proteins / metabolism* HSP90 Heat-Shock Proteins / chemistry HSP90 Heat-Shock Proteins / metabolism* Models, Molecular Protein Binding Protein Folding Protein Interaction Maps
Resource
C.elegans