Threonine 22 Phosphorylation Attenuates Hsp90 Interaction with Cochaperones and Affects Its Chaperone Activity

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• 作者：Mehdi Mollapour¹ ; ⁷ ; Shinji Tsutsumi¹ ; ⁷ ; Andrew  ; W. Truman³ ; ⁸ ; Wanping Xu¹ ; Cara  ; K. Vaughan⁴ ; Kristin Beebe¹ ; Anna Konstantinova¹ ; Srinivas Vourganti¹ ; Barry Panaretou⁵ ; Peter  ; W. Piper³ ; Jane  ; B. Trepel² ; Chrisostomos Prodromou⁶ ; Laurence  ; H. Pearl⁶ ; Len Neckers¹ ; ^{len@helix.nih.gov}
• 刊名：Molecular Cell
• 出版年：2011
• 出版时间：18 March 2011
• 年：2011
• 卷：41
• 期：6
• 页码：672-681
• 全文大小：929 K

文摘

Summary

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 b1; helix-1 of the yeast Hsp90 N-domain both in vitro and in vivo. This b1; 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.