Hsp90 is regulated by a switch point in the C-terminal domain.
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Retzlaff M, Stahl M, Eberl HC, Lagleder S, Beck J, Kessler H, Buchner J
Hsp90 is regulated by a switch point in the C-terminal domain.
EMBO Rep. 2009 Oct;10(10):1147-53. doi: 10.1038/embor.2009.153. Epub 2009 Aug 21.
- PubMed ID
- 19696785 [ View in PubMed]
- Abstract
Heat shock protein 90 (Hsp90) is an abundant, dimeric ATP-dependent molecular chaperone, and ATPase activity is essential for its in vivo functions. S-nitrosylation of a residue located in the carboxy-terminal domain has been shown to affect Hsp90 activity in vivo. To understand how variation of a specific amino acid far away from the amino-terminal ATP-binding site regulates Hsp90 functions, we mutated the corresponding residue and analysed yeast and human Hsp90 variants both in vivo and in vitro. Here, we show that this residue is a conserved, strong regulator of Hsp90 functions, including ATP hydrolysis and chaperone activity. Unexpectedly, the variants alter both the C-terminal and N-terminal association properties of Hsp90, and shift its conformational equilibrium within the ATPase cycle. Thus, S-nitrosylation of this residue allows the fast and efficient fine regulation of Hsp90.