Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity.
Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity.
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DOI：
10.1016/j.molcel.2011.02.011
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发表时间：
2011-03-18
期刊：
影响因子：
16
通讯作者：
Neckers L
中科院分区：
文献类型：
--
作者：
Mollapour M;Tsutsumi S;Truman AW;Xu W;Vaughan CK;Beebe K;Konstantinova A;Vourganti S;Panaretou B;Piper PW;Trepel JB;Prodromou C;Pearl LH;Neckers L
热休克蛋白90（Heat Shock Protein 90，Hsp 90）是一种重要的分子伴侣，其活性不仅受辅伴侣的调节，还受不同的翻译后修饰的调节。我们在此报道了酪蛋白激酶2在体外和体内磷酸化酵母Hsp 90 N-结构域α-螺旋1中保守的苏氨酸残基（T22）。该α-螺旋参与与Hsp 90中间结构域中的催化环的疏水相互作用，有助于稳定分子伴侣的ATP酶活性状态。该残基的磷酸模拟突变改变了Hsp 90 ATP酶活性和伴侣蛋白功能，并影响与辅助伴侣蛋白Aha 1和Cdc 37的相互作用。Aha 1的过表达刺激ATP酶活性，恢复共伴侣相互作用，并补偿这些Hsp 90突变体的功能缺陷。
Heat Shock Protein 90 (Hsp90) is an essential molecular chaperone whose activity is regulated not only by co-chaperones but also by distinct post-translational 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. Phospho-mimetic mutation of this residue alters Hsp90 ATPase activity and chaperone function, and impacts interaction with the co-chaperones Aha1 and Cdc37. Over-expression of Aha1 stimulates the ATPase activity, restores co-chaperone interactions, and compensates for the functional defects of these Hsp90 mutants.
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影响因子：
16.8
作者：
Mayer, Matthias P.;Prodromou, Chrisostomos;Frydman, Judith
通讯作者：
Frydman, Judith
影响因子：
16
作者：
Mollapour, Mehdi;Tsutsumi, Shinji;Donnelly, Alison C.;Beebe, Kristin;Tokita, Mari J.;Lee, Min-Jung;Lee, Sunmin;Morra, Giulia;Bourboulia, Dimitra;Scroggins, Bradley T.;Colombo, Giorgio;Blagg, Brian S.;Panaretou, Barry;Stetler-Stevenson, William G.;Trepel, Jane B.;Piper, Peter W.;Prodromou, Chrisostomos;Pearl, Laurence H.;Neckers, Len
通讯作者：
Neckers, Len
影响因子：
5.3
作者：
Hawle, Patricija;Siepmann, Martin;Obermann, Wolfgang M. J.
通讯作者：
Obermann, Wolfgang M. J.
影响因子：
2.7
作者：
Bron, Patrick;Giudice, Emmanuel;Garnier, Cyrille
通讯作者：
Garnier, Cyrille
影响因子：
16.8
作者：
Hessling, Martin;Richter, Klaus;Buchner, Johannes
通讯作者：
Buchner, Johannes