Molecular chaperones play central roles in sustaining protein homeostasis and preventing protein aggregation. Most studies of these systems have been performed in bulk, providing averaged measurements, though recent single-molecule approaches have provided an in-depth understanding of the molecular mechanisms of their activities and structural rearrangements during substrate recognition. Chaperone activities have been observed to be substrate specific, with some associated with ATP-dependent structural dynamics and others via interactions with co-chaperones. This Review aims to describe the novel mechanisms of molecular chaperones as revealed by single-molecule approaches, and to provide insights into their functioning and its implications for protein homeostasis and human diseases.

分子伴侣在维持蛋白质稳态和防止蛋白质聚集方面发挥着核心作用。对这些系统的大多数研究都是批量进行的，提供了平均测量结果，尽管最近的单分子方法已经提供了对其活性和底物识别过程中结构重排的分子机制的深入了解。据观察，伴侣分子活性具有底物特异性，其中一些与 ATP 依赖性结构动力学相关，另一些则通过与共伴侣相互作用。本综述旨在描述单分子方法揭示的分子伴侣的新机制，并深入了解其功能及其对蛋白质稳态和人类疾病的影响。