Threonine 22 Phosphorylation attenuates Hsp90 interaction with Cochaperones and affects its chaperone activity
Mollapour, M. and Tsutsumi, T. and Truman, A.W. and Xu, W. and Vaughan, Cara K. and Beebe, K. and Konstantinova, A. and Vourganti, S. and Panaretou, B. and Piper, P.W. and Trepel, J.B. and Prodromou, C. and Pearl, L.H. and Neckers, L. (2011) Threonine 22 Phosphorylation attenuates Hsp90 interaction with Cochaperones and affects its chaperone activity. Molecular Cell 41 (6), pp. 672-681. ISSN 1097-2765.
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.
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Research Centre:||Structural Molecular Biology, Institute of (ISMB)|
|Date Deposited:||18 Mar 2011 08:57|
|Last Modified:||06 Dec 2016 10:45|
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