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Activation of the DnaK-ClpB Complex is Regulated by the Properties of the Bound Substrate
dc.contributor.author | Fernández Higuero, José Ángel | |
dc.contributor.author | Aguado Martínez, Alejandra | |
dc.contributor.author | Perales Calvo, Judit | |
dc.contributor.author | Moro Pérez, Fernando | |
dc.contributor.author | Muga Villate, Arturo | |
dc.date.accessioned | 2018-06-28T08:08:24Z | |
dc.date.available | 2018-06-28T08:08:24Z | |
dc.date.issued | 2018-04-11 | |
dc.identifier.citation | Scientific Reports 8 : (2018) // Article ID 5796 | es_ES |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/10810/27765 | |
dc.description.abstract | The chaperone ClpB in bacteria is responsible for the reactivation of aggregated proteins in collaboration with the DnaK system. Association of these chaperones at the aggregate surface stimulates ATP hydrolysis, which mediates substrate remodeling. However, a question that remains unanswered is whether the bichaperone complex can be selectively activated by substrates that require remodeling. We find that large aggregates or bulky, native-like substrates activates the complex, whereas a smaller, permanently unfolded protein or extended, short peptides fail to stimulate it. Our data also indicate that ClpB interacts differently with DnaK in the presence of aggregates or small peptides, displaying a higher affinity for aggregate-bound DnaK, and that DnaK-ClpB collaboration requires the coupled ATPase-dependent remodeling activities of both chaperones. Complex stimulation is mediated by residues at the beta subdomain of DnaK substrate binding domain, which become accessible to the disaggregase when the lid is allosterically detached from the beta subdomain. Complex activation also requires an active NBD2 and the integrity of the M domain-ring of ClpB. Disruption of the M-domain ring allows the unproductive stimulation of the DnaK-ClpB complex in solution. The ability of the DnaK-ClpB complex to discriminate different substrate proteins might allow its activation when client proteins require remodeling. | es_ES |
dc.description.sponsorship | A.A. thanks the Basque Government for a Predoctoral Fellowship. The excellent technical assistance of N. Orozco is gratefully acknowledged. We also thank Mathias P. Mayer for the plasmid encoding the DnaK SBD. This work was supported by grants BFU2016-75983 (AEI/FEDER, UE) and IT709-13 (Basque Government). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU2016-75983 | |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | molecular chaperone dnak | es_ES |
dc.subject | protein aggregate reactivation | es_ES |
dc.subject | aaa plus disaggregase | es_ES |
dc.subject | exchange factor grpe | es_ES |
dc.subject | binding domain | es_ES |
dc.subject | escherichia-coli | es_ES |
dc.subject | hsp70 chaperones | es_ES |
dc.subject | structural insights | es_ES |
dc.subject | conformational dynamics | es_ES |
dc.subject | allosteric regulation | es_ES |
dc.title | Activation of the DnaK-ClpB Complex is Regulated by the Properties of the Bound Substrate | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre- ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per- mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0 | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41598-018-24140-5 | es_ES |
dc.identifier.doi | 10.1038/s41598-018-24140-5 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
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ative Commons license, and indicate if changes were made. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons license and your intended use is not per-
mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder. To view a copy of this license, visit
http://creativecommons.org/licenses/by/4.0