UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

4-19-2016

Document Type

Article

Disciplines

Biochemistry | Molecular Biology

Abstract

To probe the mechanism of the Hsp90 chaperone that is required for the maturation of many signaling proteins in eukaryotes, we analyzed the effects of all individual amino acid changes in the ATPase domain on yeast growth rate. The sensitivity of a position to mutation was strongly influenced by proximity to the phosphates of ATP, indicating that ATPase-driven conformational changes impose stringent physical constraints on Hsp90. To investigate how these constraints may vary for different clients, we performed biochemical analyses on a panel of Hsp90 mutants spanning the full range of observed fitness effects. We observed distinct effects of nine Hsp90 mutations on activation of v-src and glucocorticoid receptor (GR), indicating that different chaperone mechanisms can be utilized for these clients. These results provide a detailed guide for understanding Hsp90 mechanism and highlight the potential for inhibitors of Hsp90 that target a subset of clients.

Rights and Permissions

Citation: Cell Rep. 2016 Apr 19;15(3):588-98. doi: 10.1016/j.celrep.2016.03.046. Epub 2016 Apr 7. Link to article on publisher's site

DOI of Published Version

10.1016/j.celrep.2016.03.046

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Cell reports

PubMed ID

27068472

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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