Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Int J Mol Sci. 2023 Jan 6;24(2):1170. doi: 10.3390/ijms24021170.
The Hsp70 family of molecular chaperones acts as a central 'hub' in the cell that interacts with numerous newly synthesized proteins to assist in their biogenesis. Apart from its central and well-established role in facilitating protein folding, Hsp70s also act as key decision points in the cellular chaperone network that direct client proteins to distinct biogenesis and quality control pathways. In this paper, we review accumulating data that illustrate a new branch in the Hsp70 network: the post-translational targeting of nascent membrane and organellar proteins to diverse cellular organelles. Work in multiple pathways suggests that Hsp70, via its ability to interact with components of protein targeting and translocation machineries, can initiate elaborate substrate relays in a sophisticated cascade of chaperones, cochaperones, and receptor proteins, and thus provide a mechanism to safeguard and deliver nascent membrane proteins to the correct cellular membrane. We discuss the mechanistic principles gleaned from better-studied Hsp70-dependent targeting pathways and outline the observations and outstanding questions in less well-studied systems.
热休克蛋白 70 家族分子伴侣作为细胞中的一个中央“枢纽”，与众多新合成的蛋白质相互作用，协助其生物发生。除了在促进蛋白质折叠方面的核心和成熟作用外，Hsp70s 还作为细胞伴侣网络中的关键决策点，将客户蛋白导向不同的生物发生和质量控制途径。在本文中，我们回顾了积累的数据，这些数据说明了 Hsp70 网络的一个新分支：新生膜和细胞器蛋白向不同细胞细胞器的翻译后靶向。在多种途径中的工作表明，Hsp70 通过与蛋白靶向和易位机制组件的相互作用，能够在复杂的伴侣蛋白、共伴侣蛋白和受体蛋白级联反应中启动精细的底物传递，从而提供一种机制来保护和将新生膜蛋白递送到正确的细胞膜。我们讨论了从研究更深入的 Hsp70 依赖性靶向途径中获得的机制原理，并概述了在研究较少的系统中观察到的现象和悬而未决的问题。
