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

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...

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Autores principales:	Lukas Schmauder, Eva Absmeier, Alexander Bepperling, Katalin Barkovits, Katrin Marcus, Klaus Richter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/009ec7443080461ca0586e53266851ad
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spelling	oai:doaj.org-article:009ec7443080461ca0586e53266851ad2021-11-08T10:46:14ZNematode CDC-37 and DNJ-13 form complexes and can interact with HSP-9010.1038/s41598-021-00885-42045-2322https://doaj.org/article/009ec7443080461ca0586e53266851ad2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00885-4https://doaj.org/toc/2045-2322Abstract 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.Lukas SchmauderEva AbsmeierAlexander BepperlingKatalin BarkovitsKatrin MarcusKlaus RichterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lukas Schmauder Eva Absmeier Alexander Bepperling Katalin Barkovits Katrin Marcus Klaus Richter Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90
description	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.
format	article
author	Lukas Schmauder Eva Absmeier Alexander Bepperling Katalin Barkovits Katrin Marcus Klaus Richter
author_facet	Lukas Schmauder Eva Absmeier Alexander Bepperling Katalin Barkovits Katrin Marcus Klaus Richter
author_sort	Lukas Schmauder
title	Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90
title_short	Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90
title_full	Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90
title_fullStr	Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90
title_full_unstemmed	Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90
title_sort	nematode cdc-37 and dnj-13 form complexes and can interact with hsp-90
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/009ec7443080461ca0586e53266851ad
work_keys_str_mv	AT lukasschmauder nematodecdc37anddnj13formcomplexesandcaninteractwithhsp90 AT evaabsmeier nematodecdc37anddnj13formcomplexesandcaninteractwithhsp90 AT alexanderbepperling nematodecdc37anddnj13formcomplexesandcaninteractwithhsp90 AT katalinbarkovits nematodecdc37anddnj13formcomplexesandcaninteractwithhsp90 AT katrinmarcus nematodecdc37anddnj13formcomplexesandcaninteractwithhsp90 AT klausrichter nematodecdc37anddnj13formcomplexesandcaninteractwithhsp90
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Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90

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