Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition
A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, polyubiquitins are found in different arrangements of ubiquitin subunits. To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target reco...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
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eLife Sciences Publications Ltd
2015-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/05767 |
| _version_ | 1811200340260814848 |
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| author | Zhu Liu Zhou Gong Wen-Xue Jiang Ju Yang Wen-Kai Zhu Da-Chuan Guo Wei-Ping Zhang Mai-Li Liu Chun Tang |
| author_facet | Zhu Liu Zhou Gong Wen-Xue Jiang Ju Yang Wen-Kai Zhu Da-Chuan Guo Wei-Ping Zhang Mai-Li Liu Chun Tang |
| author_sort | Zhu Liu |
| collection | DOAJ |
| description | A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, polyubiquitins are found in different arrangements of ubiquitin subunits. To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target recognition mechanism, we characterize the conformational space of Lys63-linked diubiquitin (K63-Ub2). Refining against inter-subunit paramagnetic NMR data, we show that free K63-Ub2 exists as a dynamic ensemble comprising multiple closed and open quaternary states. The quaternary dynamics enables K63-Ub2 to be specifically recognized in a variety of signaling pathways. When binding to a target protein, one of the preexisting quaternary states is selected and stabilized. A point mutation that shifts the equilibrium between the different states modulates the binding affinities towards K63-Ub2 ligands. This conformational selection mechanism at the quaternary level may be used by polyubiquitins of different lengths and linkages for target recognition. |
| first_indexed | 2024-04-12T02:03:14Z |
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| id | doaj.art-36fcb550b8e14f86ba81195e229438b0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:03:14Z |
| publishDate | 2015-06-01 |
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| spelling | doaj.art-36fcb550b8e14f86ba81195e229438b02022-12-22T03:52:37ZengeLife Sciences Publications LtdeLife2050-084X2015-06-01410.7554/eLife.05767Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognitionZhu Liu0Zhou Gong1Wen-Xue Jiang2Ju Yang3Wen-Kai Zhu4Da-Chuan Guo5Wei-Ping Zhang6Mai-Li Liu7Chun Tang8https://orcid.org/0000-0001-6477-6500CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China; Department of Pharmacology and Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, ChinaCAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, ChinaCAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, ChinaCAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, ChinaCAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, ChinaCAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, ChinaDepartment of Pharmacology and Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, ChinaCAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, ChinaCAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, ChinaA polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, polyubiquitins are found in different arrangements of ubiquitin subunits. To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target recognition mechanism, we characterize the conformational space of Lys63-linked diubiquitin (K63-Ub2). Refining against inter-subunit paramagnetic NMR data, we show that free K63-Ub2 exists as a dynamic ensemble comprising multiple closed and open quaternary states. The quaternary dynamics enables K63-Ub2 to be specifically recognized in a variety of signaling pathways. When binding to a target protein, one of the preexisting quaternary states is selected and stabilized. A point mutation that shifts the equilibrium between the different states modulates the binding affinities towards K63-Ub2 ligands. This conformational selection mechanism at the quaternary level may be used by polyubiquitins of different lengths and linkages for target recognition.https://elifesciences.org/articles/05767polyubiquitindynamicsensembleNMRparamagnetic |
| spellingShingle | Zhu Liu Zhou Gong Wen-Xue Jiang Ju Yang Wen-Kai Zhu Da-Chuan Guo Wei-Ping Zhang Mai-Li Liu Chun Tang Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition eLife polyubiquitin dynamics ensemble NMR paramagnetic |
| title | Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition |
| title_full | Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition |
| title_fullStr | Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition |
| title_full_unstemmed | Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition |
| title_short | Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition |
| title_sort | lys63 linked ubiquitin chain adopts multiple conformational states for specific target recognition |
| topic | polyubiquitin dynamics ensemble NMR paramagnetic |
| url | https://elifesciences.org/articles/05767 |
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