Weak intra-ring allosteric communications of the archaeal chaperonin thermosome revealed by normal mode analysis.

Weak intra-ring allosteric communications of the archaeal chaperonin thermosome revealed by normal mode analysis.
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正态模式分析揭示了古菌伴侣蛋白热体的环内变构通讯较弱。

DOI:
10.1016/j.bpj.2012.07.049
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发表时间:
2012
影响因子:
3.4
通讯作者:
Stan,George
Stan,George
中科院分区:
生物学3区
文献类型:
--
作者:
Jayasinghe,Manori;Shrestha,Pooja;Wu,Xiongwu;Tehver,Riina;Stan,George

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分子伴侣是一种分子机器,它使用ATP驱动的循环来帮助错误折叠的底物蛋白质达到自然状态。在功能周期中,这些机器采用不同的核苷酸依赖的构象状态,反映了个别亚基的大规模变构变化。不同的变构动力学已被描述为这两类伴侣。细菌(I组)伴侣蛋白,如GroEL,在每个环内经历协调的亚基运动,而古生物和真核生物伴侣蛋白(II组)经历连续的亚单位运动。我们通过对古生物伴侣蛋白、热粒和GroEL的单体和双环结构的比较正常模式分析来研究这些不同的机制。我们发现,每种类型的热粒单体都表现出常见的简正模的低频行为。观察到的不同的高频模式归因于这些亚单位类型的功能专门化。正如在GroEL情况下所发现的那样,热粒双环结构对高频模的贡献更大。我们发现,在热体环中,氨基酸对的长程亚基间相关性比在GroEL中弱。总体而言,我们的结果表明,这两类伴侣的不同变构行为源于单个亚基和亚基间通讯的不同连接。
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.
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