Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90

Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90

Blog Article

Abstract The molecular chaperones Hsc70 and Hsp90 are required Specialty Pipes 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 threadheaders.shop 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.