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

Tsutsumi, Shinji, Mollapour, Mehdi, Graf, Christian, Lee, Chung-Tien, Scroggins, Bradley T., Xu, Wanping, Haslerova, Lenka, Hessling, Martin, Konstantinova, Anna A., Trepel, Jane B., and others. (2009) Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain. Nature Structural and Molecular Biology, 16 (11). pp. 1141-1147. ISSN 1545-9985. (doi:10.1038/nsmb.1682) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:40379)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL: http://dx.doi.org/10.1038/nsmb.1682

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.

Item Type:	Article
DOI/Identification number:	10.1038/nsmb.1682
Additional information:	Mollapour designated joint first author; number of additional authors: 14;
Subjects:	Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Divisions:	Divisions > Division of Natural Sciences > Biosciences
Depositing User:	Stewart Brownrigg
Date Deposited:	07 Mar 2014 00:05 UTC
Last Modified:	05 Nov 2024 10:24 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/40379 (The current URI for this page, for reference purposes)

University of Kent Author Information

Mollapour, Mehdi.

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