Pearl Laurence H, Prodromou Chrisostomos
Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom.
Annu Rev Biochem. 2006;75:271-94. doi: 10.1146/annurev.biochem.75.103004.142738.
Heat shock protein 90 (Hsp90) is a molecular chaperone essential for activating many signaling proteins in the eukaryotic cell. Biochemical and structural analysis of Hsp90 has revealed a complex mechanism of ATPase-coupled conformational changes and interactions with cochaperone proteins, which facilitate activation of Hsp90's diverse "clientele." Despite recent progress, key aspects of the ATPase-coupled mechanism of Hsp90 remain controversial, and the nature of the changes, engendered by Hsp90 in client proteins, is largely unknown. Here, we discuss present knowledge of Hsp90 structure and function gleaned from crystallographic studies of individual domains and recent progress in obtaining a structure for the ATP-bound conformation of the intact dimeric chaperone. Additionally, we describe the roles of the plethora of cochaperones with which Hsp90 cooperates and growing insights into their biochemical mechanisms, which come from crystal structures of Hsp90 cochaperone complexes.
热休克蛋白90（Hsp90）是一种分子伴侣，对于激活真核细胞中的许多信号蛋白至关重要。对Hsp90的生化和结构分析揭示了一种与ATP酶偶联的构象变化以及与共伴侣蛋白相互作用的复杂机制，这有助于激活Hsp90的多种“客户”蛋白。尽管最近取得了进展，但Hsp90与ATP酶偶联机制的关键方面仍存在争议，并且Hsp90在客户蛋白中引起的变化性质在很大程度上尚不清楚。在这里，我们讨论了从单个结构域的晶体学研究中获得的关于Hsp90结构和功能的现有知识，以及在获得完整二聚体伴侣蛋白的ATP结合构象结构方面的最新进展。此外，我们描述了与Hsp90合作的大量共伴侣蛋白的作用，以及对它们生化机制的日益深入的了解，这些了解来自Hsp90共伴侣蛋白复合物的晶体结构。
