This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Johnson, J. L.
Right arrow Articles by Flom, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Johnson, J. L.
Right arrow Articles by Flom, G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2007, p. 768-776, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01034-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Nucleotide-Dependent Interaction of Saccharomyces cerevisiae Hsp90 with the Cochaperone Proteins Sti1, Cpr6, and Sba1{triangledown}

Jill L. Johnson,* Agnieszka Halas, and Gary Flom

Department of Microbiology, Molecular Biology and Biochemistry and Center for Reproductive Biology, University of Idaho, Moscow, Idaho 83844-3052

Received 8 June 2006/ Returned for modification 24 July 2006/ Accepted 30 October 2006

The ATP-dependent molecular chaperone Hsp90 and partner cochaperone proteins are required for the folding and activity of diverse cellular client proteins, including steroid hormone receptors and multiple oncogenic kinases. Hsp90 undergoes nucleotide-dependent conformational changes, but little is known about how these changes are coupled to client protein activation. In order to clarify how nucleotides affect Hsp90 interactions with cochaperone proteins, we monitored assembly of wild-type and mutant Hsp90 with Sti1, Sba1, and Cpr6 in Saccharomyces cerevisiae cell extracts. Wild-type Hsp90 bound Sti1 in a nucleotide-independent manner, while Sba1 and Cpr6 specifically and independently interacted with Hsp90 in the presence of the nonhydrolyzable analog of ATP, AMP-PNP. Alterations in Hsp90 residues that contribute to ATP binding or hydrolysis prevented or altered Sba1 and Cpr6 interaction; additional alterations affected the specificity of Cpr6 interaction. Some mutant forms of Hsp90 also displayed reduced Sti1 interaction in the presence of a nucleotide. These studies indicate that cycling of Hsp90 between the nucleotide-free, open conformation and the ATP-bound, closed conformation is influenced by residues both within and outside the N-terminal ATPase domain and that these conformational changes have dramatic effects on interaction with cochaperone proteins.

* Corresponding author. Mailing address: Department of Microbiology, Molecular Biology and Biochemistry and Center for Reproductive Biology, University of Idaho, Moscow, Idaho 83844-3052. Phone: (208) 885-9767. Fax: (208) 885-6518. E-mail: jilljohn{at}uidaho.edu.

{triangledown} Published ahead of print on 13 November 2006.

Molecular and Cellular Biology, January 2007, p. 768-776, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01034-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Forafonov, F., Toogun, O. A., Grad, I., Suslova, E., Freeman, B. C., Picard, D. (2008). p23/Sba1p Protects against Hsp90 Inhibitors Independently of Its Intrinsic Chaperone Activity. Mol. Cell. Biol. 28: 3446-3456 [Abstract] [Full Text]  
  • Toogun, O. A., DeZwaan, D. C., Freeman, B. C. (2008). The Hsp90 Molecular Chaperone Modulates Multiple Telomerase Activities. Mol. Cell. Biol. 28: 457-467 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»