1. Academic Validation
  2. Hsp90 is regulated by a switch point in the C-terminal domain

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.
Marco Retzlaff 1 Michael Stahl H Christian Eberl Stephan Lagleder Jürgen Beck Horst Kessler Johannes Buchner
Affiliations

Affiliation

  • 1 Center for Integrated Protein Science, Department of Chemistry, Technische Universität München, Garching, Germany.
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.

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