Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.
Exp Biol Med (Maywood). 2021 Jun;246(12):1419-1434. doi: 10.1177/1535370221999812. Epub 2021 Mar 17.
The chaperone heat shock protein 70 (Hsp70) and its network of co-chaperones serve as a central hub of cellular protein quality control mechanisms. Domain organization in Hsp70 dictates ATPase activity, ATP dependent allosteric regulation, client/substrate binding and release, and interactions with co-chaperones. The protein quality control activities of Hsp70 are classified as foldase, holdase, and disaggregase activities. Co-chaperones directly assisting protein refolding included J domain proteins and nucleotide exchange factors. However, co-chaperones can also be grouped and explored based on which domain of Hsp70 they interact. Here we discuss how the network of cytosolic co-chaperones for Hsp70 contributes to the functions of Hsp70 while closely looking at their structural features. Comparison of domain organization and the structures of co-chaperones enables greater understanding of the interactions, mechanisms of action, and roles played in protein quality control.
伴侣热休克蛋白 70（Hsp70）及其伴侣蛋白网络作为细胞蛋白质量控制机制的核心枢纽。Hsp70 的结构域组织决定了 ATP 酶活性、ATP 依赖性变构调节、客户/底物结合和释放以及与伴侣蛋白的相互作用。Hsp70 的蛋白质量控制活性可分为折叠酶、持留酶和去聚集酶活性。直接协助蛋白重折叠的伴侣蛋白包括 J 结构域蛋白和核苷酸交换因子。然而，根据它们与 Hsp70 的哪个结构域相互作用，伴侣蛋白也可以进行分组和探索。在这里，我们讨论了细胞质伴侣蛋白网络如何为 Hsp70 的功能做出贡献，同时密切关注它们的结构特征。比较结构域组织和伴侣蛋白的结构可以更好地理解相互作用、作用机制以及在蛋白质量控制中所扮演的角色。
