The Plasticity of the Hsp90 Co-chaperone System
The Plasticity of the Hsp90 Co-chaperone System
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DOI：
10.1016/j.molcel.2017.08.004
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发表时间：
2017-09-21
期刊：
影响因子：
16
通讯作者：
Buchner, Johannes
中科院分区：
文献类型：
--
作者：
Sahasrabudhe, Priyanka;Rohrberg, Julia;Buchner, Johannes
真核细胞胞质溶胶中的Hsp 90系统的特征在于结合Hsp 90并影响其功能的一组共分子伴侣。虽然已经取得了进展，关于潜在的生化机制，如何辅分子伴侣影响Hsp 90客户蛋白在体内仍然难以捉摸。通过研究12个Hsp 90辅助分子伴侣对酵母中不同客户蛋白活性的影响，我们发现辅助分子伴侣的缺失可以对客户活性产生中性或负面影响，但也可以导致更活跃的客户。只有少数共同监护人对所有研究的客户都很活跃。密切相关的客户端甚至点突变体可以依赖于不同的辅助分子伴侣。这些影响是直接的，因为客户端-共分子伴侣相互作用的差异可以在体外重建。有趣的是，一些辅助分子伴侣在体内影响客户构象。因此，辅分子伴侣使Hsp 90循环适应客户蛋白的要求，确保最佳活化。
The Hsp90 system in the eukaryotic cytosol is characterized by a cohort of co-chaperones that bind to Hsp90 and affect its function. Although progress has been made regarding the underlying biochemical mechanisms, how co-chaperones influence Hsp90 client proteins in vivo has remained elusive. By investigating the effect of 12 Hsp90 co-chaperones on the activity of different client proteins in yeast, we find that deletion of co-chaperones can have a neutral or negative effect on client activity but can also lead to more active clients. Only a few co-chaperones are active on all clients studied. Closely related clients and even point mutants can depend on different co-chaperones. These effects are direct because differences in client-co-chaperone interactions can be reconstituted in vitro. Interestingly, some co-chaperones affect client conformation in vivo. Thus, co-chaperones adapt the Hsp90 cycle to the requirements of the client proteins, ensuring optimal activation.