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

journal contribution
posted on 2023-06-08, 18:34 authored by Mehdi Mollapour, Shinji Tsutsumi, Andrew W Truman, Wanping Xu, Cara K Vaughan, Kristin Beebe, Anna Konstantinova, Srinivas Vourganti, Barry Panaretou, Peter W Piper, Jane B Trepel, Chrisostomos ProdromouChrisostomos Prodromou, Laurence PearlLaurence Pearl, Len Neckers
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 a helix-1 of the yeast Hsp90 N-domain both in vitro and in vivo. This a 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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular Cell

ISSN

1097-2765

Publisher

Elsevier

Issue

6

Volume

41

Page range

672-681

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2014-09-30

First Compliant Deposit (FCD) Date

2014-09-30

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