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The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be di...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10480186/ https://www.ncbi.nlm.nih.gov/pubmed/37670029 http://dx.doi.org/10.1038/s41467-023-41150-8 |
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author | Velasco-Carneros, Lorea Cuéllar, Jorge Dublang, Leire Santiago, César Maréchal, Jean-Didier Martín-Benito, Jaime Maestro, Moisés Fernández-Higuero, José Ángel Orozco, Natalia Moro, Fernando Valpuesta, José María Muga, Arturo |
author_facet | Velasco-Carneros, Lorea Cuéllar, Jorge Dublang, Leire Santiago, César Maréchal, Jean-Didier Martín-Benito, Jaime Maestro, Moisés Fernández-Higuero, José Ángel Orozco, Natalia Moro, Fernando Valpuesta, José María Muga, Arturo |
author_sort | Velasco-Carneros, Lorea |
collection | PubMed |
description | J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. The J-domains are accessible to Hsc70 within the tubular structure. They allow binding of closely spaced Hsc70 molecules that could be transferred to the unfolded substrate for its cooperative remodelling, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70. |
format | Online Article Text |
id | pubmed-10480186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104801862023-09-07 The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70 Velasco-Carneros, Lorea Cuéllar, Jorge Dublang, Leire Santiago, César Maréchal, Jean-Didier Martín-Benito, Jaime Maestro, Moisés Fernández-Higuero, José Ángel Orozco, Natalia Moro, Fernando Valpuesta, José María Muga, Arturo Nat Commun Article J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. The J-domains are accessible to Hsc70 within the tubular structure. They allow binding of closely spaced Hsc70 molecules that could be transferred to the unfolded substrate for its cooperative remodelling, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70. Nature Publishing Group UK 2023-09-05 /pmc/articles/PMC10480186/ /pubmed/37670029 http://dx.doi.org/10.1038/s41467-023-41150-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access 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 Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Velasco-Carneros, Lorea Cuéllar, Jorge Dublang, Leire Santiago, César Maréchal, Jean-Didier Martín-Benito, Jaime Maestro, Moisés Fernández-Higuero, José Ángel Orozco, Natalia Moro, Fernando Valpuesta, José María Muga, Arturo The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70 |
title | The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70 |
title_full | The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70 |
title_fullStr | The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70 |
title_full_unstemmed | The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70 |
title_short | The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70 |
title_sort | self-association equilibrium of dnaja2 regulates its interaction with unfolded substrate proteins and with hsc70 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10480186/ https://www.ncbi.nlm.nih.gov/pubmed/37670029 http://dx.doi.org/10.1038/s41467-023-41150-8 |
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