Center for integrated Protein Science Munich (CiPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
Center for integrated Protein Science Munich (CiPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
Biochim Biophys Acta Mol Cell Res. 2018 Jun;1865(6):889-897. doi: 10.1016/j.bbamcr.2018.03.008. Epub 2018 Mar 18.
Hsp90 is a highly conserved and abundant chaperone. It participates in essential cellular activities by supporting the maturation process of its client proteins, many of which are protein kinases and steroid receptors. Client processing is achieved via extensive conformational changes within the dimeric chaperone. This requires an ATP hydrolysis activity that is controlled by auto-inhibitory mechanisms and several structurally diverse cofactors. Especially the client-specificity of Hsp90 depends on client-specific cofactors, which can adapt Hsp90's activities to the client requirements at different conditions and in different cell types. Additionally, post-translational modifications can influence almost every aspect of Hsp90's interactions and activities. In this review, we present these regulatory principles, discuss the factors that have an impact on Hsp90's function and elaborate the mechanisms that are responsible for regulating the Hsp90 machinery.
热休克蛋白 90（Hsp90）是一种高度保守且丰富的伴侣蛋白。它通过支持其客户蛋白的成熟过程参与基本的细胞活动，其中许多客户蛋白是蛋白激酶和甾体受体。通过二聚体伴侣蛋白内的广泛构象变化实现客户处理。这需要一种由自动抑制机制和几种结构不同的辅助因子控制的 ATP 水解活性。特别是 Hsp90 的客户特异性取决于客户特异性辅助因子，这些辅助因子可以使 Hsp90 的活性适应不同条件和不同细胞类型的客户需求。此外，翻译后修饰几乎可以影响 Hsp90 相互作用和活性的各个方面。在这篇综述中，我们介绍了这些调节原则，讨论了影响 Hsp90 功能的因素，并详细阐述了负责调节 Hsp90 机制的机制。
