State-dependent sequential allostery exhibited by chaperonin TRiC/CCT revealed by network analysis of Cryo-EM maps.
State-dependent sequential allostery exhibited by chaperonin TRiC/CCT revealed by network analysis of Cryo-EM maps.
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状态依赖性顺序变构表现出伴侣蛋白TRiC/CCT揭示了网络分析的冷冻-EM地图。
DOI：
10.1016/j.pbiomolbio.2020.08.006
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发表时间：
2021-03
影响因子：
3.8
通讯作者：
Bahar I
中科院分区：
文献类型：
--
作者：
Zhang Y;Krieger J;Mikulska-Ruminska K;Kaynak B;Sorzano COS;Carazo JM;Xing J;Bahar I
真核生物伴侣蛋白TRiC/CCT在通过ATP驱动的变构循环辅助许多蛋白质折叠中起主要作用。最近的结构阐明冷冻电子显微镜提供了一个广阔的视野的构象访问的伴侣蛋白周期的各个阶段，包括一个连续的激活其亚基在响应核苷酸结合。但我们缺乏对TRiC/CCT机制的基础结构动力学和通信特性的彻底机械理解。在这项研究中，我们提出了一种计算方法的基础上适应cryo-EM密度图的弹性网络模型，以获得更深入的了解结构编码的变构动力学的十六进制机器。我们已经分析了几种结构的伴侣蛋白解决在不同的状态映射其构象景观。我们的研究表明，整体架构本质上有利于合作运动，符合实验中观察到的结构变异。此外，个体亚基CCT 1-CCT 8在变构循环的不同状态下表现出状态依赖性顺序事件。例如，在ATP结合状态下，亚基CCT 5和CCT 4选择性地启动整体结构所支持的盖闭合运动;而在异聚体的载脂蛋白形式中，亚基CCT 7表现出对结构变化的最高倾向。然后，这些变化通过平行的变构信号流传播到两个环上的邻居。预测的顺序激活的状态依赖机制提供了新的见解TRiC/CCT环内和环间信号转导事件。
The eukaryotic chaperonin TRiC/CCT plays a major role in assisting the folding of many proteins through an ATP-driven allosteric cycle. Recent structures elucidated by cryo-electron microscopy provide a broad view of the conformations visited at various stages of the chaperonin cycle, including a sequential activation of its subunits in response to nucleotide binding. But we lack a thorough mechanistic understanding of the structure-based dynamics and communication properties that underlie the TRiC/CCT machinery. In this study, we present a computational methodology based on elastic network models adapted to cryo-EM density maps to gain a deeper understanding of the structure-encoded allosteric dynamics of this hexadecameric machine. We have analysed several structures of the chaperonin resolved in different states toward mapping its conformational landscape. Our study indicates that the overall architecture intrinsically favours cooperative movements that comply with the structural variabilities observed in experiments. Furthermore, the individual subunits CCT1-CCT8 exhibit state-dependent sequential events at different states of the allosteric cycle. For example, in the ATP-bound state, subunits CCT5 and CCT4 selectively initiate the lid closure motions favoured by the overall architecture; whereas in the apo form of the heteromer, the subunit CCT7 exhibits the highest predisposition to structural change. The changes then propagate through parallel fluxes of allosteric signals to neighbours on both rings. The predicted state-dependent mechanisms of sequential activation provide new insights into TRiC/CCT intra- and inter-ring signal transduction events.
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影响因子：
6.8
作者：
Cossio, Pilar;Hummer, Gerhard
通讯作者：
Hummer, Gerhard
影响因子：
9.9
作者：
通讯作者：
--
影响因子：
5.6
作者：
Beuron, F;Flynn, TC;Freemont, PS
通讯作者：
Freemont, PS
DOI：
10.1016/s1359-0278(97)00024-2
发表时间：
1997-01-01
期刊：
FOLDING & DESIGN
影响因子：
--
作者：
Bahar, I;Atilgan, AR;Erman, B
通讯作者：
Erman, B
影响因子：
3
作者：
Bernardi, Rafael C.;Melo, Marcelo C. R.;Schulten, Klaus
通讯作者：
Schulten, Klaus