Nucleotide-dependent interaction of Saccharomyces cerevisiae Hsp90 with the cochaperone proteins Sti1, Cpr6, and Sba1

Jill L Johnson; Agnieszka Halas; Gary Flom

doi:10.1128/MCB.01034-06

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Nucleotide-dependent interaction of Saccharomyces cerevisiae Hsp90 with the cochaperone proteins Sti1, Cpr6, and Sba1

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Nucleotide-dependent interaction of Saccharomyces cerevisiae Hsp90 with the cochaperone proteins Sti1, Cpr6, and Sba1

Jill L Johnson, Agnieszka Halas and Gary Flom

Molecular and cellular biology, Vol.27(2), pp.768-776

01/2007

DOI: https://doi.org/10.1128/MCB.01034-06

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https://hdl.handle.net/2376/109733

PMCID: PMC1800796

PMID: 17101799

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Abstract

Molecular Chaperones - metabolism

Saccharomyces cerevisiae - genetics

Cyclophilins - metabolism

Saccharomyces cerevisiae Proteins - genetics

Saccharomyces cerevisiae - metabolism

Adenylyl Imidodiphosphate - metabolism

Heat-Shock Proteins

Saccharomyces cerevisiae Proteins - metabolism

HSP90 Heat-Shock Proteins - metabolism

Protein Binding

Protein Conformation

HSP90 Heat-Shock Proteins - genetics

Mutation

Dimerization

Fungal Proteins - metabolism

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.

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Title: Nucleotide-dependent interaction of Saccharomyces cerevisiae Hsp90 with the cochaperone proteins Sti1, Cpr6, and Sba1
Creators: Jill L Johnson - Department of Microbiology, Molecular Biology and Biochemistry and Center for Reproductive Biology, University of Idaho, Moscow, ID 83844-3052, USA. jilljohn@uidaho.edu
Agnieszka Halas
Gary Flom
Publication Details: Molecular and cellular biology, Vol.27(2), pp.768-776
Academic Unit: UNKNOWN
Publisher: United States
Grant note: P20 RR 15587 / NCRR NIH HHS P20 RR015587 / NCRR NIH HHS
Identifiers: 99900547387501842
Language: English
Resource Type: Journal article