dc.contributor.author | Cabrera Hernández, Yovana ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.contributor.author | Bernardo Seisdedos, Ganeko | |
dc.contributor.author | Dublang Irazabal, Leire ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.contributor.author | Albesa Jové, David | |
dc.contributor.author | Orozco, Natalia | |
dc.contributor.author | Viguera Rincón, Ana Rosa | |
dc.contributor.author | Millet Aguilar-Galindo, Oscar | |
dc.contributor.author | Muga Villate, Arturo ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.contributor.author | Moro Pérez, Fernando ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.date.accessioned | 2022-12-19T17:20:20Z | |
dc.date.available | 2022-12-19T17:20:20Z | |
dc.date.issued | 2022-11 | |
dc.identifier.citation | Journal of Molecular Biology 434(22) : (2022) // Article ID 167841 | es_ES |
dc.identifier.issn | 0022-2836 | |
dc.identifier.issn | 1089-8638 | |
dc.identifier.uri | http://hdl.handle.net/10810/58886 | |
dc.description.abstract | Apg2, one of the three cytosolic Hsp110 chaperones in humans, supports reactivation of unordered and ordered protein aggregates by Hsc70 (HspA8). Together with DnaJB1, Apg2 serves to nucleate Hsc70 molecules into sites where productive entropic pulling forces can be developed. During aggregate reac-tivation, Apg2 performs as a specialized nucleotide exchange factor, but the origin of its specialization is poorly defined. Here we report on the role of the distinctive C-terminal extension present in Apg2 and other metazoan homologs. We found that the first part of this Apg2 subdomain, with propensity to adopt a-helical structure, interacts with the nucleotide binding domain of Hsc70 in a nucleotide -dependent manner, contributing significantly to the stability of the Hsc70:Apg2 complex. Moreover, the second intrinsically disordered segment of Apg2 C-terminal extension plays an important role as a down -regulator of nucleotide exchange. An NMR analysis showed that the interaction with Hsc70 nucleotide binding domain modifies the chemical environment of residues located in important functional sites such as the interface between lobe I and II and the nucleotide binding site. Our data indicate that Apg2 C -terminal extension is a fine-tuner of human Hsc70 activity that optimizes the substrate remodeling ability of the chaperone system. | es_ES |
dc.description.sponsorship | This work was supported by CTQ2016-76941-R (MINECO), Fundacion BiofisicaBizkaia, the Basque Excellence Research Centre(BERC) of the Basque Government and Fundacion BBVA to D.A.-J., and BFU2016-75983-P and PID2019-111068 GB-100 (MCI/AEI/FEDER, UE)grants from Spanish Government to A.M. and F.M.and IT1745-22 from Basque Government to F.M. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/CTQ2016-76941-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU2016-75983-P | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-111068 GB-100 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Hsc70 | es_ES |
dc.subject | Apg2 | es_ES |
dc.subject | chaperone complex | es_ES |
dc.subject | chaperone regulation | es_ES |
dc.subject | protein aggregation | es_ES |
dc.title | Fine-tuning of the Hsc70-based Human Protein Disaggregase Machinery by the Distinctive C-terminal Extension of Apg2 | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2022 The Author(s). Published by Elsevier Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/). | es_ES |
dc.rights.holder | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0022283622004612?via%3Dihub | es_ES |
dc.identifier.doi | 10.1016/j.jmb.2022.167841 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |