Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, HBNI, Kolkata, India.
IUBMB Life. 2017 Sep;69(9):647-659. doi: 10.1002/iub.1656. Epub 2017 Jul 27.
Molecular chaperones are one of the key players in protein biology and as such their structure and mechanism of action have been extensively studied. However the substrate specificity of molecular chaperones has not been well investigated. This review aims to summarize what is known about the substrate specificity and substrate recognition motifs of chaperones so as to better understand what substrate specificity means in the context of molecular chaperones. Available literature shows that the majority of chaperones have broad substrate range and recognize non-native conformations of proteins depending on recognition of hydrophobic and/or charged patches. Based on these recognition motifs chaperones can select for early, mid or late folding intermediates. Another major contributor to chaperone specificity are the co-chaperones they interact with as well as the sub-cellular location they are expressed in and the inducability of their expression. Some chaperones which have only one or a few known substrates are reported. In their case the mode of recognition seems to be specific structural complementarity between chaperone and substrate. It can be concluded that the vast majority of chaperones do not show a high degree of specificity but recognize elements that signal non-native protein conformation and their substrate range is modulated by the context they function in. However a few chaperones are known that display exquisite specificity of their substrate e.g. mammalian heat shock protein 47 collagen interaction. © 2017 IUBMB Life, 69(9):647-659, 2017.
分子伴侣是蛋白质生物学中的关键参与者之一，因此它们的结构和作用机制已经得到了广泛的研究。然而，分子伴侣的底物特异性尚未得到很好的研究。本文旨在总结分子伴侣的底物特异性和底物识别基序的已知内容，以便更好地理解分子伴侣中底物特异性的含义。现有文献表明，大多数伴侣具有广泛的底物范围，并根据对疏水性和/或带电斑块的识别来识别蛋白质的非天然构象。基于这些识别基序，伴侣可以选择早期、中期或晚期折叠中间体。伴侣特异性的另一个主要贡献者是它们相互作用的共伴侣，以及它们表达的亚细胞位置和表达的诱导能力。据报道，一些只具有一个或几个已知底物的伴侣。在这种情况下，识别模式似乎是伴侣和底物之间特异性的结构互补性。可以得出结论，绝大多数伴侣并没有表现出高度的特异性，而是识别那些信号非天然蛋白质构象的元件，并且它们的底物范围受到它们所处的环境的调节。然而，已经知道一些伴侣对其底物表现出极高的特异性，例如哺乳动物热休克蛋白 47 与胶原蛋白的相互作用。
