Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Struct Mol Biol. 2009 Nov;16(11):1141-7. doi: 10.1038/nsmb.1682. Epub 2009 Oct 18.

Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain.

Author information

  • 1Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.

Abstract

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.

PMID:
19838189
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk