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

Mollapour, Mehdi, Tsutsumi, Shinji, Truman, Andrew W, Xu, Wanping, Vaughan, Cara K, Beebe, Kristin, Konstantinova, Anna, Vourganti, Srinivas, Panaretou, Barry, Piper, Peter W, Trepel, Jane B, Prodromou, Chrisostomos, 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

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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 α helix-1 of the yeast Hsp90 N-domain both in vitro and in vivo. This α 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
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Q Science > QP Physiology > QP0501 Animal biochemistry
Depositing User: Laurence Pearl
Date Deposited: 30 Sep 2014 12:24
Last Modified: 08 Mar 2017 08:30
URI: http://sro.sussex.ac.uk/id/eprint/50441

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