Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90
Abstract The molecular chaperone and heat shock protein Hsp90 is part of many protein complexes in eukaryotic cells. Together with its cochaperones, Hsp90 is responsible for the maturation of hundreds of clients. Although having been investigated for decades, it still is largely unknown which compon...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-44847-6 |
| _version_ | 1797349809272651776 |
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| author | Leonie Vollmar Julia Schimpf Bianca Hermann Thorsten Hugel |
| author_facet | Leonie Vollmar Julia Schimpf Bianca Hermann Thorsten Hugel |
| author_sort | Leonie Vollmar |
| collection | DOAJ |
| description | Abstract The molecular chaperone and heat shock protein Hsp90 is part of many protein complexes in eukaryotic cells. Together with its cochaperones, Hsp90 is responsible for the maturation of hundreds of clients. Although having been investigated for decades, it still is largely unknown which components are necessary for a functional complex and how the energy of ATP hydrolysis is used to enable cyclic operation. Here we use single-molecule FRET to show how cochaperones introduce directionality into Hsp90’s conformational changes during its interaction with the client kinase Ste11. Three cochaperones are needed to couple ATP turnover to these conformational changes. All three are therefore essential for a functional cyclic operation, which requires coupling to an energy source. Finally, our findings show how the formation of sub-complexes in equilibrium followed by a directed selection of the functional complex can be the most energy efficient pathway for kinase maturation. |
| first_indexed | 2024-03-08T12:36:49Z |
| format | Article |
| id | doaj.art-ca71ecee9e37442fb07085e45b75683b |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T12:36:49Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-ca71ecee9e37442fb07085e45b75683b2024-01-21T12:27:18ZengNature PortfolioNature Communications2041-17232024-01-0115111110.1038/s41467-024-44847-6Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90Leonie Vollmar0Julia Schimpf1Bianca Hermann2Thorsten Hugel3Institute of Physical Chemistry, University of FreiburgInstitute of Physical Chemistry, University of FreiburgInstitute of Physical Chemistry, University of FreiburgInstitute of Physical Chemistry, University of FreiburgAbstract The molecular chaperone and heat shock protein Hsp90 is part of many protein complexes in eukaryotic cells. Together with its cochaperones, Hsp90 is responsible for the maturation of hundreds of clients. Although having been investigated for decades, it still is largely unknown which components are necessary for a functional complex and how the energy of ATP hydrolysis is used to enable cyclic operation. Here we use single-molecule FRET to show how cochaperones introduce directionality into Hsp90’s conformational changes during its interaction with the client kinase Ste11. Three cochaperones are needed to couple ATP turnover to these conformational changes. All three are therefore essential for a functional cyclic operation, which requires coupling to an energy source. Finally, our findings show how the formation of sub-complexes in equilibrium followed by a directed selection of the functional complex can be the most energy efficient pathway for kinase maturation.https://doi.org/10.1038/s41467-024-44847-6 |
| spellingShingle | Leonie Vollmar Julia Schimpf Bianca Hermann Thorsten Hugel Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90 Nature Communications |
| title | Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90 |
| title_full | Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90 |
| title_fullStr | Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90 |
| title_full_unstemmed | Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90 |
| title_short | Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90 |
| title_sort | cochaperones convey the energy of atp hydrolysis for directional action of hsp90 |
| url | https://doi.org/10.1038/s41467-024-44847-6 |
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