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.

中文翻译：

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磷酸化诱导的陪伴酮解折叠促进激酶募集和客户类别特异性Hsp90磷酸化。

在Hsp90介导的蛋白激酶分子伴侣化过程中，该机制的核心成分Hsp90和伴侣蛋白Cdc37在调节伴侣蛋白周期进程的不同磷酸化状态之间循环。我们显示，在Y298处的Cdc37磷酸化导致C末端结构域的部分展开和折叠中间体的种群。展开通过揭露磷酸肽序列而促进了Y197处Hsp90的磷酸化，该序列用作通过其SH2结构域将非受体酪氨酸激酶募集到伴侣复合物中的停靠位点。反过来，Y197处的Hsp90磷酸化特异性调节其与Cdc37的相互作用，因此仅影响蛋白激酶客户的伴侣。总而言之，我们发现通过提供客户端类特定性，