Department of Chemistry, Northern Kentucky University, Highland Heights, Kentucky, USA.
Biophys J. 2012 Sep 19;103(6):1285-95. doi: 10.1016/j.bpj.2012.07.049.
Chaperonins are molecular machines that use ATP-driven cycles to assist misfolded substrate proteins to reach the native state. During the functional cycle, these machines adopt distinct nucleotide-dependent conformational states, which reflect large-scale allosteric changes in individual subunits. Distinct allosteric kinetics has been described for the two chaperonin classes. Bacterial (group I) chaperonins, such as GroEL, undergo concerted subunit motions within each ring, whereas archaeal and eukaryotic chaperonins (group II) undergo sequential subunit motions. We study these distinct mechanisms through a comparative normal mode analysis of monomer and double-ring structures of the archaeal chaperonin thermosome and GroEL. We find that thermosome monomers of each type exhibit common low-frequency behavior of normal modes. The observed distinct higher-frequency modes are attributed to functional specialization of these subunit types. The thermosome double-ring structure has larger contribution from higher-frequency modes, as it is found in the GroEL case. We find that long-range intersubunit correlation of amino-acid pairs is weaker in the thermosome ring than in GroEL. Overall, our results indicate that distinct allosteric behavior of the two chaperonin classes originates from different wiring of individual subunits as well as of the intersubunit communications.
伴侣蛋白是一种分子机器，它利用 ATP 驱动的循环来帮助错误折叠的底物蛋白达到天然状态。在功能循环中，这些机器采用不同的核苷酸依赖构象状态，反映了单个亚基的大规模变构变化。两种伴侣蛋白类都有不同的变构动力学描述。细菌（I 组）伴侣蛋白，如 GroEL，在每个环内发生协同的亚基运动，而古菌和真核生物伴侣蛋白（II 组）则发生顺序的亚基运动。我们通过对古菌伴侣蛋白热体素和 GroEL 的单体和双环结构进行比较的正则模态分析来研究这些不同的机制。我们发现每种类型的热体素单体都表现出正则模态的常见低频行为。观察到的不同高频模式归因于这些亚基类型的功能专业化。热体素双环结构具有更高频模式的更大贡献，因为它与 GroEL 情况相同。我们发现，与 GroEL 相比，热体素环中亚基之间的氨基酸对的长程相互作用较弱。总的来说，我们的结果表明，两种伴侣蛋白类的不同变构行为源于单个亚基以及亚基间通讯的不同布线。
