Phosphorylation induced cochaperone unfolding promotes kinase recruitment and client class-specific Hsp90 phosphorylation.
Phosphorylation induced cochaperone unfolding promotes kinase recruitment and client class-specific Hsp90 phosphorylation.
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磷酸化诱导的联酮展开促进激酶募集和客户类特异性HSP90磷酸化。
DOI：
10.1038/s41467-017-02711-w
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发表时间：
2018-01-17
影响因子：
16.6
通讯作者：
Gelis I
中科院分区：
文献类型：
--
作者：
Bachman AB;Keramisanou D;Xu W;Beebe K;Moses MA;Vasantha Kumar MV;Gray G;Noor RE;van der Vaart A;Neckers L;Gelis I
在热休克蛋白90介导的蛋白激酶的伴侣，机器的核心组件，热休克蛋白90和cochaperone Cdc 37，在不同的磷酸化状态，调节伴侣循环的进展之间循环。我们发现Cdc 37在Y298的磷酸化导致C-末端结构域和折叠中间体的部分展开。解折叠通过暴露磷酸肽序列来促进Hsp 90在Y197处的磷酸化，磷酸肽序列作为对接位点，通过其SH 2结构域将非受体酪氨酸激酶募集到伴侣复合物中。反过来，在Y197处的Hsp 90磷酸化特异性地调节其与Cdc 37的相互作用，从而仅影响蛋白激酶客户的伴侣作用。总之，我们发现，通过提供客户类别特异性，Hsp 90协同分子（例如Cdc 37）不仅有助于客户招募，而且还以客户类别特异性的方式塑造Hsp 90的翻译后修饰格局。热休克蛋白90分子伴侣循环受到多种磷酸化事件的影响，但其调控功能知之甚少。在这里，作者表明，磷酸化和解折叠的cochaperone Cdc 37裁缝的热休克蛋白90伴侣周期通过招募激酶，促进不同的磷酸化模式。
During the Hsp90-mediated chaperoning of protein kinases, the core components of the machinery, Hsp90 and the cochaperone Cdc37, recycle between different phosphorylation states that regulate progression of the chaperone cycle. We show that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal domain and the population of folding intermediates. Unfolding facilitates Hsp90 phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a docking site to recruit non-receptor tyrosine kinases to the chaperone complex via their SH2 domains. In turn, Hsp90 phosphorylation at Y197 specifically regulates its interaction with Cdc37 and thus affects the chaperoning of only protein kinase clients. In summary, we find that by providing client class specificity, Hsp90 cochaperones such as Cdc37 do not merely assist in client recruitment but also shape the post-translational modification landscape of Hsp90 in a client class-specific manner. The Hsp90 chaperone cycle is influenced by multiple phosphorylation events but their regulatory functions are poorly understood. Here, the authors show that phosphorylation and unfolding of cochaperone Cdc37 tailors the Hsp90 chaperone cycle by recruiting kinases that promote distinct phosphorylation patterns.
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影响因子：
64.5
作者：
Kirschke E;Goswami D;Southworth D;Griffin PR;Agard DA
通讯作者：
Agard DA
影响因子：
2.7
作者：
d'Auvergne EJ;Gooley PR
通讯作者：
Gooley PR
影响因子：
64.8
作者：
ECK, MJ;SHOELSON, SE;HARRISON, SC
通讯作者：
HARRISON, SC
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML