分子伴侣的主要类别具有高度可变的序列,尺寸,和形状,然而它们都与展开的蛋白质结合,限制它们的聚集,并协助他们的折叠。尽管这个过程对蛋白质稳态至关重要,尚不清楚伴侣如何指导这一过程,或者伴侣的不同家族是否使用类似的机制。第一次,核磁共振波谱的最新进展使人们能够详细研究如何展开,“客户”蛋白质与ATP依赖性和ATP非依赖性伴侣相互作用。这里,我们回顾了四个不同伴侣的例子,间谍,触发因子,DnaK,和HscA-HscB,强调它们机制之间的异同。一个惊人的相似之处是,监护人都与他们的客户弱绑定,这样伴侣与客户的互动很容易被更强的人所竞争,折叠状态下的分子内和分子间接触。因此,这些相互作用相对较弱的亲和力似乎为折叠过程提供了方向性。然而,也有关键的区别,特别是在伴侣如何释放客户以及ATP循环如何影响该过程的细节中。例如,间谍以折叠状态释放客户,而客户端似乎在从触发因子或DnaK释放后展开。一起,这些研究开始揭示伴侣如何利用弱相互作用指导蛋白质折叠的异同。
The major classes of molecular chaperones have highly variable sequences, sizes, and shapes, yet they all bind to unfolded proteins, limit their aggregation, and assist in their folding. Despite the central importance of this process to protein homeostasis, it has not been clear exactly how chaperones guide this process or whether the diverse families of chaperones use similar mechanisms. For the first time, recent advances in NMR spectroscopy have enabled detailed studies of how unfolded, \"client\" proteins interact with both ATP-dependent and ATP-independent classes of chaperones. Here, we review examples from four distinct chaperones, Spy, Trigger Factor, DnaK, and HscA-HscB, highlighting the similarities and differences between their mechanisms. One striking similarity is that the chaperones all bind weakly to their clients, such that the chaperone-client interactions are readily outcompeted by stronger, intra- and intermolecular contacts in the folded state. Thus, the relatively weak affinity of these interactions seems to provide directionality to the folding process. However, there are also key differences, especially in the details of how the chaperones release clients and how ATP cycling impacts that process. For example, Spy releases clients in a largely folded state, while clients seem to be unfolded upon release from Trigger Factor or DnaK. Together, these studies are beginning to uncover the similarities and differences in how chaperones use weak interactions to guide protein folding.