Hsp90 is regulated by a switch point in the C-terminal domain.

نویسندگان

  • Marco Retzlaff
  • Michael Stahl
  • H Christian Eberl
  • Stephan Lagleder
  • Jürgen Beck
  • Horst Kessler
  • Johannes Buchner
چکیده

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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عنوان ژورنال:
  • EMBO reports

دوره 10 10  شماره 

صفحات  -

تاریخ انتشار 2009