Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity

Mollapour, Mehdi and Tsutsumi, Shinji and Truman, Andrew W. and Xu, Wanping and Vaughan, Cara K. and Beebee, Kirstin and Kostantinova, Anna and Vourganti, Srinivas and Panaretou, Barry and Piper, Peter W. and Trepel, Jane B. and Prodromou, Chrisostomos and Pearl, Laurence H. and Neckers, Len (2011) Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity. Molecular Cell, 41 (6). pp. 672-681. ISSN 1097-2765. (doi:https://doi.org/10.1016/j.molcel.2011.02.011) (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)

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Official URL
http://dx.doi.org/10.1016/j.molcel.2011.02.011

Abstract

Heat shock protein 90 (Hsp90) is an essential molecular chaperone whose activity is regulated not only by cochaperones but also by distinct posttranslational modifications. We report here that casein kinase 2 phosphorylates a conserved threonine residue (T22) in ? helix-1 of the yeast Hsp90 N-domain both in vitro and in vivo. This ? helix participates in a hydrophobic interaction with the catalytic loop in Hsp90's middle domain, helping to stabilize the chaperone's ATPase-competent state. Phosphomimetic mutation of this residue alters Hsp90 ATPase activity and chaperone function and impacts interaction with the cochaperones Aha1 and Cdc37. Overexpression of Aha1 stimulates the ATPase activity, restores cochaperone interactions, and compensates for the functional defects of these Hsp90 mutants.

Item Type: Article
Additional information: number of additional authors: 13;
Subjects: Q Science
R Medicine
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Stewart Brownrigg
Date Deposited: 07 Mar 2014 00:05 UTC
Last Modified: 09 Jul 2014 15:37 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/40377 (The current URI for this page, for reference purposes)
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