Division of Biology, California Institute of Technology, Pasadena, CA, USA.
Biomed J. 2013 May-Jun;36(3):106-17. doi: 10.4103/2319-4170.113230.
Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.
热休克蛋白 90（Hsp90）是一种依赖于 ATP 的分子伴侣，在真核生物中必不可少。它对于多种客户蛋白的激活和稳定是必需的，其中许多蛋白参与重要的细胞途径。由于 Hsp90 影响众多生理过程，如信号转导、细胞内运输和蛋白质降解，因此它成为癌症治疗的一个有趣靶点。在结构上，Hsp90 是一种由三个不同结构域组成的灵活二聚体蛋白，这些结构域采用结构上不同的构象。ATP 结合引发这些构象变化的方向性，并导致更紧凑的状态。为了实现其功能，Hsp90 与一大组辅助因子（称为共伴侣）一起工作。共伴侣与 Hsp90 形成定义明确的二元或三元复合物，促进客户蛋白的成熟。此外，Hsp90 的翻译后修饰，如磷酸化和乙酰化，提供了另一个调节水平。它们影响构象循环、共伴侣相互作用和域间通信。在这篇综述中，我们讨论了在理解 Hsp90 机制方面取得的最新进展。
