Correlation Engine 2.0
Clear Search sequence regions

Sizes of these terms reflect their relevance to your search.

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.


Bettina K Zierer, Martin Rübbelke, Franziska Tippel, Tobias Madl, Florian H Schopf, Daniel A Rutz, Klaus Richter, Michael Sattler, Johannes Buchner. Importance of cycle timing for the function of the molecular chaperone Hsp90. Nature structural & molecular biology. 2016 Nov;23(11):1020-1028

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 27723736

View Full Text