School of Biological Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia; Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.
School of Chemistry, University of Wollongong, Wollongong, New South Wales 2522, Australia; Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.
J Mol Biol. 2018 Oct 26;430(22):4525-4546. doi: 10.1016/j.jmb.2018.05.021. Epub 2018 May 19.
The heat-shock proteins (Hsp) are a family of molecular chaperones, which collectively form a network that is critical for the maintenance of protein homeostasis. Traditional ensemble-based measurements have provided a wealth of knowledge on the function of individual Hsps and the Hsp network; however, such techniques are limited in their ability to resolve the heterogeneous, dynamic and transient interactions that molecular chaperones make with their client proteins. Single-molecule techniques have emerged as a powerful tool to study dynamic biological systems, as they enable rare and transient populations to be identified that would usually be masked in ensemble measurements. Thus, single-molecule techniques are particularly amenable for the study of Hsps and have begun to be used to reveal novel mechanistic details of their function. In this review, we discuss the current understanding of the chaperone action of Hsps and how gaps in the field can be addressed using single-molecule methods. Specifically, this review focuses on the ATP-independent small Hsps and the broader Hsp network and describes how these dynamic systems are amenable to single-molecule techniques.
热休克蛋白（Hsp）是分子伴侣家族，它们共同形成了一个网络，对维持蛋白质的内稳态至关重要。传统的基于整体的测量方法为单个 Hsp 和 Hsp 网络的功能提供了丰富的知识；然而，这些技术在解析分子伴侣与其客户蛋白质之间的异质、动态和瞬时相互作用方面存在局限性。单分子技术已成为研究动态生物系统的有力工具，因为它们能够识别通常在整体测量中被掩盖的稀有和瞬时群体。因此，单分子技术特别适合研究 Hsp，并已开始用于揭示其功能的新机制细节。在这篇综述中，我们讨论了对 Hsp 伴侣作用的现有理解，以及如何使用单分子方法解决该领域的空白。具体来说，这篇综述集中在非 ATP 依赖的小 Hsp 和更广泛的 Hsp 网络，并描述了这些动态系统如何适合单分子技术。
