Document Detail


Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain.
MedLine Citation:
PMID:  19838189     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heat 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.
Authors:
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 Prodromou; Len Neckers
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2009-10-18
Journal Detail:
Title:  Nature structural & molecular biology     Volume:  16     ISSN:  1545-9985     ISO Abbreviation:  Nat. Struct. Mol. Biol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-05     Completed Date:  2009-11-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101186374     Medline TA:  Nat Struct Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1141-7     Citation Subset:  IM    
Affiliation:
Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs / genetics,  physiology
Animals
COS Cells
Cercopithecus aethiops
Enzyme-Linked Immunosorbent Assay
Fluorescence Resonance Energy Transfer
HSP90 Heat-Shock Proteins / chemistry*,  genetics,  metabolism*
Humans
Hydrophobicity*
Immunoblotting
Immunoprecipitation
Mutation
Protein Binding / genetics
Protein Structure, Tertiary
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/HSP90 Heat-Shock Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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