Booth Christopher R, Meyer Anne S, Cong Yao, Topf Maya, Sali Andrej, Ludtke Steven J, Chiu Wah, Frydman Judith
Graduate Program in Structural and Computational Biology and Molecular Biophysics, One Baylor Plaza, Baylor College of Medicine, Houston, Texas 77030, USA.
Nat Struct Mol Biol. 2008 Jul;15(7):746-53. doi: 10.1038/nsmb.1436. Epub 2008 Jun 8.
All chaperonins mediate ATP-dependent polypeptide folding by confining substrates within a central chamber. Intriguingly, the eukaryotic chaperonin TRiC (also called CCT) uses a built-in lid to close the chamber, whereas prokaryotic chaperonins use a detachable lid. Here we determine the mechanism of lid closure in TRiC using single-particle cryo-EM and comparative protein modeling. Comparison of TRiC in its open, nucleotide-free, and closed, nucleotide-induced states reveals that the interdomain motions leading to lid closure in TRiC are radically different from those of prokaryotic chaperonins, despite their overall structural similarity. We propose that domain movements in TRiC are coordinated through unique interdomain contacts within each subunit and, further, these contacts are absent in prokaryotic chaperonins. Our findings show how different mechanical switches can evolve from a common structural framework through modification of allosteric networks.
所有伴侣蛋白都通过将底物限制在中央腔室内来介导依赖ATP的多肽折叠。有趣的是，真核伴侣蛋白TRiC（也称为CCT）使用内置盖子关闭腔室，而原核伴侣蛋白则使用可拆卸盖子。在这里，我们使用单颗粒冷冻电镜和比较蛋白质建模来确定TRiC中盖子关闭的机制。对处于开放、无核苷酸状态和关闭、核苷酸诱导状态的TRiC进行比较发现，尽管TRiC和原核伴侣蛋白的整体结构相似，但导致TRiC中盖子关闭的结构域间运动与原核伴侣蛋白的运动截然不同。我们提出，TRiC中的结构域运动是通过每个亚基内独特的结构域间接触来协调的，而且原核伴侣蛋白中不存在这些接触。我们的研究结果表明，不同的机械开关如何通过变构网络的修饰从共同的结构框架进化而来。
