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Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle
The co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes the closed conformation of Hsp90, inhibits its ATPase and is important for client maturation. Yet, how this is achieved has remained enigmatic. Here, we show that a tryptophan residue in the proximal region of the tail dece...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864943/ https://www.ncbi.nlm.nih.gov/pubmed/33547294 http://dx.doi.org/10.1038/s41467-021-21063-0 |
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author | Biebl, Maximilian M. Lopez, Abraham Rehn, Alexandra Freiburger, Lee Lawatscheck, Jannis Blank, Birgit Sattler, Michael Buchner, Johannes |
author_facet | Biebl, Maximilian M. Lopez, Abraham Rehn, Alexandra Freiburger, Lee Lawatscheck, Jannis Blank, Birgit Sattler, Michael Buchner, Johannes |
author_sort | Biebl, Maximilian M. |
collection | PubMed |
description | The co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes the closed conformation of Hsp90, inhibits its ATPase and is important for client maturation. Yet, how this is achieved has remained enigmatic. Here, we show that a tryptophan residue in the proximal region of the tail decelerates the ATPase by allosterically switching the conformation of the catalytic loop in Hsp90. We further show by NMR spectroscopy that the tail interacts with the Hsp90 client binding site via a conserved helix. This helical motif in the p23 tail also binds to the client protein glucocorticoid receptor (GR) in the free and Hsp90-bound form. In vivo experiments confirm the physiological importance of ATPase modulation and the role of the evolutionary conserved helical motif for GR activation in the cellular context. |
format | Online Article Text |
id | pubmed-7864943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78649432021-02-16 Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle Biebl, Maximilian M. Lopez, Abraham Rehn, Alexandra Freiburger, Lee Lawatscheck, Jannis Blank, Birgit Sattler, Michael Buchner, Johannes Nat Commun Article The co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes the closed conformation of Hsp90, inhibits its ATPase and is important for client maturation. Yet, how this is achieved has remained enigmatic. Here, we show that a tryptophan residue in the proximal region of the tail decelerates the ATPase by allosterically switching the conformation of the catalytic loop in Hsp90. We further show by NMR spectroscopy that the tail interacts with the Hsp90 client binding site via a conserved helix. This helical motif in the p23 tail also binds to the client protein glucocorticoid receptor (GR) in the free and Hsp90-bound form. In vivo experiments confirm the physiological importance of ATPase modulation and the role of the evolutionary conserved helical motif for GR activation in the cellular context. Nature Publishing Group UK 2021-02-05 /pmc/articles/PMC7864943/ /pubmed/33547294 http://dx.doi.org/10.1038/s41467-021-21063-0 Text en © The Author(s) 2021 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 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 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Biebl, Maximilian M. Lopez, Abraham Rehn, Alexandra Freiburger, Lee Lawatscheck, Jannis Blank, Birgit Sattler, Michael Buchner, Johannes Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle |
title | Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle |
title_full | Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle |
title_fullStr | Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle |
title_full_unstemmed | Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle |
title_short | Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle |
title_sort | structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the hsp90 chaperone cycle |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864943/ https://www.ncbi.nlm.nih.gov/pubmed/33547294 http://dx.doi.org/10.1038/s41467-021-21063-0 |
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