Center for Integrated Protein Science at the Department of Chemistry, Technische Universität München, 85748 Garching, Germany.
Center for Integrated Protein Science at the Department of Chemistry, Technische Universität München, 85748 Garching, Germany.
Mol Cell. 2017 Sep 21;67(6):947-961.e5. doi: 10.1016/j.molcel.2017.08.004. Epub 2017 Sep 7.
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.
真核细胞质中的 Hsp90 系统的特点是存在一群共伴侣蛋白，它们与 Hsp90 结合并影响其功能。尽管在基础生化机制方面已经取得了进展，但共伴侣蛋白如何影响 Hsp90 客户蛋白在体内的活性仍然难以捉摸。通过研究 12 种 Hsp90 共伴侣蛋白对酵母中不同客户蛋白活性的影响，我们发现共伴侣蛋白的缺失对客户蛋白的活性可能没有影响，也可能导致更活跃的客户蛋白。只有少数共伴侣蛋白对所有研究的客户蛋白都具有活性。密切相关的客户蛋白甚至点突变体可能依赖于不同的共伴侣蛋白。这些效应是直接的，因为在体外可以重建客户-共伴侣蛋白相互作用的差异。有趣的是，一些共伴侣蛋白在体内影响客户蛋白的构象。因此，共伴侣蛋白使 Hsp90 循环适应客户蛋白的要求，确保最佳激活。
