| Ubiquitin chain conformation regulates recognition and activity of interacting proteins. | |
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MedLine Citation:
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PMID: 23201676 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mechanisms of protein recognition have been extensively studied for single-domain proteins, but are less well characterized for dynamic multidomain systems. Ubiquitin chains represent a biologically important multidomain system that requires recognition by structurally diverse ubiquitin-interacting proteins. Ubiquitin chain conformations in isolation are often different from conformations observed in ubiquitin-interacting protein complexes, indicating either great dynamic flexibility or extensive chain remodelling upon binding. Using single-molecule fluorescence resonance energy transfer, we show that Lys 63-, Lys 48- and Met 1-linked diubiquitin exist in several distinct conformational states in solution. Lys 63- and Met 1-linked diubiquitin adopt extended 'open' and more compact 'closed' conformations, and ubiquitin-binding domains and deubiquitinases (DUBs) select pre-existing conformations. By contrast, Lys 48-linked diubiquitin adopts predominantly compact conformations. DUBs directly recognize existing conformations, but may also remodel ubiquitin chains to hydrolyse the isopeptide bond. Disruption of the Lys 48-diubiquitin interface changes conformational dynamics and affects DUB activity. Hence, conformational equilibria in ubiquitin chains provide an additional layer of regulation in the ubiquitin system, and distinct conformations observed in differently linked polyubiquitin may contribute to the specificity of ubiquitin-interacting proteins. |
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Authors:
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Yu Ye; Georg Blaser; Mathew H Horrocks; Maria J Ruedas-Rama; Shehu Ibrahim; Alexander A Zhukov; Angel Orte; David Klenerman; Sophie E Jackson; David Komander |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-12-02 |
Journal Detail:
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Title: Nature Volume: 492 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-13 Completed Date: 2012-12-21 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
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Languages: eng Pagination: 266-70 Citation Subset: IM |
Affiliation:
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Division of Protein and Nucleic Acids Chemistry, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Fluorescence Resonance Energy Transfer Models, Molecular* Protein Binding Protein Structure, Tertiary Ubiquitin / chemistry*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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U105192732//Medical Research Council; //Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
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0/Ubiquitin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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