The dynamic triage interplay of Hsp90 with its chaperone cycle and client binding
Abstract Hsp90, a crucial molecular chaperone, regulates diverse client proteins, impacting both normal biology and disease. Central to its function is its conformational plasticity, driven by ATPase activity and client interactions. However, comprehensive insights into Hsp90’s dynamic molecular tra...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55026-y |
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| _version_ | 1846121812277067776 |
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| author | Xiaozhan Qu Simin Wang Shuo Zhao Chanjuan Wan Weiya Xu Chengdong Huang |
| author_facet | Xiaozhan Qu Simin Wang Shuo Zhao Chanjuan Wan Weiya Xu Chengdong Huang |
| author_sort | Xiaozhan Qu |
| collection | DOAJ |
| description | Abstract Hsp90, a crucial molecular chaperone, regulates diverse client proteins, impacting both normal biology and disease. Central to its function is its conformational plasticity, driven by ATPase activity and client interactions. However, comprehensive insights into Hsp90’s dynamic molecular transitions remain elusive. Using solution NMR spectroscopy, we reveal how ATP binding, hydrolysis, and client engagement drive conformational and dynamic shifts in E. coli Hsp90, HtpG, through its chaperone cycle. Pronounced conformational fluctuations occur, especially in regions crucial for nucleotide binding and conformational transitions. ATP binding induces slow-exchanging conformations, representing discrete on-path transition states from open to closed forms, while ATP hydrolysis shifts HtpG into a compact conformation. Client binding acts as an allosteric switch, dynamically priming HtpG for elevated chaperone activity and, therefore, its efficient remodeling. Here, we provide atomic-level insights into Hsp90’s functional mechanism, highlighting the interplay of conformation, dynamics, nucleotide, and client interactions. |
| format | Article |
| id | doaj-art-b07cc6094f224bc68f9bb45b064c9b19 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b07cc6094f224bc68f9bb45b064c9b192024-12-15T12:10:00ZengNature PortfolioNature Communications2041-17232024-12-0115111210.1038/s41467-024-55026-yThe dynamic triage interplay of Hsp90 with its chaperone cycle and client bindingXiaozhan Qu0Simin Wang1Shuo Zhao2Chanjuan Wan3Weiya Xu4Chengdong Huang5MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at the Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at the Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at the Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at the Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at the Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at the Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaAbstract Hsp90, a crucial molecular chaperone, regulates diverse client proteins, impacting both normal biology and disease. Central to its function is its conformational plasticity, driven by ATPase activity and client interactions. However, comprehensive insights into Hsp90’s dynamic molecular transitions remain elusive. Using solution NMR spectroscopy, we reveal how ATP binding, hydrolysis, and client engagement drive conformational and dynamic shifts in E. coli Hsp90, HtpG, through its chaperone cycle. Pronounced conformational fluctuations occur, especially in regions crucial for nucleotide binding and conformational transitions. ATP binding induces slow-exchanging conformations, representing discrete on-path transition states from open to closed forms, while ATP hydrolysis shifts HtpG into a compact conformation. Client binding acts as an allosteric switch, dynamically priming HtpG for elevated chaperone activity and, therefore, its efficient remodeling. Here, we provide atomic-level insights into Hsp90’s functional mechanism, highlighting the interplay of conformation, dynamics, nucleotide, and client interactions.https://doi.org/10.1038/s41467-024-55026-y |
| spellingShingle | Xiaozhan Qu Simin Wang Shuo Zhao Chanjuan Wan Weiya Xu Chengdong Huang The dynamic triage interplay of Hsp90 with its chaperone cycle and client binding Nature Communications |
| title | The dynamic triage interplay of Hsp90 with its chaperone cycle and client binding |
| title_full | The dynamic triage interplay of Hsp90 with its chaperone cycle and client binding |
| title_fullStr | The dynamic triage interplay of Hsp90 with its chaperone cycle and client binding |
| title_full_unstemmed | The dynamic triage interplay of Hsp90 with its chaperone cycle and client binding |
| title_short | The dynamic triage interplay of Hsp90 with its chaperone cycle and client binding |
| title_sort | dynamic triage interplay of hsp90 with its chaperone cycle and client binding |
| url | https://doi.org/10.1038/s41467-024-55026-y |
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