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Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain
journal contribution
posted on 2023-06-08, 00:49 authored by Shinji Tsutsumi, Mehdi Mollapour, Christian Graf, Chung-Tien Lee, Bradley T Scroggins, Wanping Xu, Lenka Haslerova, Martin Hessling, Anna A Konstantinova, Jane B Trepel, Barry Panaretou, Johannes Buchner, Matthias P Mayer, Chrisostomos ProdromouChrisostomos Prodromou, Len NeckersHeat shock protein 90 (Hsp90) is an essential molecular chaperone in eukaryotes, as it regulates diverse signal transduction nodes that integrate numerous environmental cues to maintain cellular homeostasis. Hsp90 also is secreted from normal and transformed cells and regulates cell motility. Here, we have identified a conserved hydrophobic motif in a beta-strand at the boundary between the N domain and charged linker of Hsp90, whose mutation not only abrogated Hsp90 secretion but also inhibited its function. These Hsp90 mutants lacked chaperone activity in vitro and failed to support yeast viability. Notably, truncation of the charged linker reduced solvent accessibility of this beta-strand and restored chaperone activity to these mutants. These data underscore the importance of beta-strand 8 for Hsp90 function and demonstrate that the functional consequences of weakened hydrophobic contacts in this region are reversed by charged-linker truncation.
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Publication status
- Published
Journal
Nature Structural and Molecular BiologyISSN
1545-9993Publisher
Nature Publishing GroupExternal DOI
Issue
11Volume
16Page range
1141-1147Department affiliated with
- Biochemistry Publications
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- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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