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 |
|