Title |
Importance of cycle timing for the function of the molecular chaperone Hsp90
|
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Published in |
Nature Structural & Molecular Biology, October 2016
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DOI | 10.1038/nsmb.3305 |
Pubmed ID | |
Authors |
Bettina K Zierer, Martin Rübbelke, Franziska Tippel, Tobias Madl, Florian H Schopf, Daniel A Rutz, Klaus Richter, Michael Sattler, Johannes Buchner |
Abstract |
Hsp90 couples ATP hydrolysis to large conformational changes essential for activation of client proteins. The structural transitions involve dimerization of the N-terminal domains and formation of 'closed states' involving the N-terminal and middle domains. Here, we used Hsp90 mutants that modulate ATPase activity and biological function as probes to address the importance of conformational cycling for Hsp90 activity. We found no correlation between the speed of ATP turnover and the in vivo activity of Hsp90: some mutants with almost normal ATPase activity were lethal, and some mutants with lower or undetectable ATPase activity were viable. Our analysis showed that it is crucial for Hsp90 to attain and spend time in certain conformational states: a certain dwell time in open states is required for optimal processing of client proteins, whereas a prolonged population of closed states has negative effects. Thus, the timing of conformational transitions is crucial for Hsp90 function and not cycle speed. |
X Demographics
Geographical breakdown
Country | Count | As % |
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France | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 77 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 15 | 19% |
Researcher | 12 | 16% |
Student > Bachelor | 10 | 13% |
Student > Master | 6 | 8% |
Professor | 5 | 6% |
Other | 9 | 12% |
Unknown | 20 | 26% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 38 | 49% |
Chemistry | 5 | 6% |
Agricultural and Biological Sciences | 4 | 5% |
Medicine and Dentistry | 3 | 4% |
Unspecified | 1 | 1% |
Other | 3 | 4% |
Unknown | 23 | 30% |