Department of Biology, Stanford University, Stanford, CA 94305-5020, USA.
Cell. 2011 Jan 21;144(2):240-52. doi: 10.1016/j.cell.2010.12.017.
Group II chaperonins are ATP-dependent ring-shaped complexes that bind nonnative polypeptides and facilitate protein folding in archaea and eukaryotes. A built-in lid encapsulates substrate proteins within the central chaperonin chamber. Here, we describe the fate of the substrate during the nucleotide cycle of group II chaperonins. The chaperonin substrate-binding sites are exposed, and the lid is open in both the ATP-free and ATP-bound prehydrolysis states. ATP hydrolysis has a dual function in the folding cycle, triggering both lid closure and substrate release into the central chamber. Notably, substrate release can occur in the absence of a lid, and lid closure can occur without substrate release. However, productive folding requires both events, so that the polypeptide is released into the confined space of the closed chamber where it folds. Our results show that ATP hydrolysis coordinates the structural and functional determinants that trigger productive folding.
II 组分子伴侣是依赖于 ATP 的环形复合物，可结合非天然多肽并促进古菌和真核生物中的蛋白质折叠。内置的盖子将底物蛋白封装在中央分子伴侣腔内。在这里，我们描述了 II 组分子伴侣核苷酸循环过程中底物的命运。在无 ATP 和 ATP 结合的预水解状态下，分子伴侣的底物结合位点暴露，盖子打开。ATP 水解在折叠循环中具有双重功能，既能触发盖子关闭，又能将底物释放到中央腔内。值得注意的是，即使没有盖子，底物也可以释放，而盖子也可以在没有底物释放的情况下关闭。然而，有效的折叠需要这两个事件，这样多肽就会被释放到封闭腔的受限空间中进行折叠。我们的结果表明，ATP 水解协调了触发有效折叠的结构和功能决定因素。
