State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
Acta Biochim Biophys Sin (Shanghai). 2014 May;46(5):347-56. doi: 10.1093/abbs/gmt152. Epub 2014 Jan 20.
Small heat-shock proteins (sHSPs) are ubiquitous ATP-independent molecular chaperones that play crucial roles in protein quality control in cells. They are able to prevent the aggregation and/or inactivation of various non-native substrate proteins and assist the refolding of these substrates independently or under the help of other ATP-dependent chaperones. Substrate recognition and binding by sHSPs are essential for their chaperone functions. This review focuses on what natural substrate proteins an sHSP protects and how it binds the substrates in cells under fluctuating conditions. It appears that sHSPs of prokaryotes, although being able to bind a wide range of cellular proteins, preferentially protect certain classes of functional proteins, such as translation-related proteins and metabolic enzymes, which may well explain why they could increase the resistance of host cells against various stresses. Mechanistically, the sHSPs of prokaryotes appear to possess numerous multi-type substrate-binding residues and are able to hierarchically activate these residues in a temperature-dependent manner, and thus act as temperature-regulated chaperones. The mechanism of hierarchical activation of substrate-binding residues is also discussed regarding its implication for eukaryotic sHSPs.
小分子热休克蛋白（sHSPs）是普遍存在的、ATP 非依赖性的分子伴侣，在细胞内的蛋白质质量控制中发挥着至关重要的作用。它们能够防止各种非天然底物蛋白的聚集和/或失活，并独立或在其他 ATP 依赖性伴侣的帮助下协助这些底物的重折叠。sHSPs 对底物的识别和结合对于其伴侣功能至关重要。本综述重点讨论了 sHSP 保护哪些天然底物蛋白，以及在波动条件下它如何在细胞中结合这些底物。似乎原核生物的 sHSP 虽然能够结合广泛的细胞蛋白，但优先保护某些功能蛋白类别，如与翻译相关的蛋白质和代谢酶，这可能很好地解释了它们为什么能够提高宿主细胞对各种应激的抵抗力。从机制上讲，原核生物的 sHSP 似乎具有许多多类型的底物结合残基，并能够以温度依赖的方式对这些残基进行层次激活，从而充当温度调节伴侣。还讨论了底物结合残基的层次激活机制，及其对真核 sHSP 的意义。
