Rehn Alexandra Beatrice, Buchner Johannes
Department Chemie, Technische Universität München, Munich, Germany,
Subcell Biochem. 2015;78:113-31. doi: 10.1007/978-3-319-11731-7_6.
Hsp90 is a conserved molecular chaperone and is responsible for the folding and activation of several hundred client proteins, involved in various cellular processes. The large number and the diversity of these client proteins demand a high adaptiveness of Hsp90 towards the need of the individual client. This adaptiveness is amongst others mediated by more than 20 so-called cochaperones that differ in their actions towards Hsp90. Some of these cochaperones are able to modulate the ATPase activity of Hsp90 and/or its client protein binding, folding and activation. p23 and Aha1 are two prominent examples with opposing effects on the ATPase activity of Hsp90. p23 is able to inhibit the ATP turnover while Aha1 is the strongest known activator of the ATPase activity of Hsp90. Even though both cochaperones are conserved from yeast to man and have been studied for years, some Hsp90-related as well as Hsp90-independent functions are still enigmatic and under current investigation. In this chapter, we first introduce the ATPase cycle of Hsp90 and then focus on the two cochaperones integrating them in the Hsp90 cycle.
热休克蛋白90（Hsp90）是一种保守的分子伴侣，负责数百种客户蛋白的折叠和激活，这些客户蛋白参与各种细胞过程。这些客户蛋白的数量众多且具有多样性，这就要求Hsp90对单个客户的需求具有高度适应性。这种适应性在一定程度上是由20多种所谓的共伴侣介导的，它们对Hsp90的作用各不相同。其中一些共伴侣能够调节Hsp90的ATP酶活性和/或其与客户蛋白的结合、折叠及激活。p23和Aha1是对Hsp90的ATP酶活性具有相反作用的两个突出例子。p23能够抑制ATP周转，而Aha1是已知最强的Hsp90 ATP酶活性激活剂。尽管这两种共伴侣从酵母到人类都是保守的，并且已经研究多年，但一些与Hsp90相关以及不依赖Hsp90的功能仍然是谜，目前正在研究中。在本章中，我们首先介绍Hsp90的ATP酶循环，然后重点关注这两种共伴侣，并将它们整合到Hsp90循环中。
