Coupling between global dynamics and signal transduction pathways: a mechanism of allostery for chaperonin GroEL
Coupling between global dynamics and signal transduction pathways: a mechanism of allostery for chaperonin GroEL
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DOI：
10.1039/b717819k
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Bahar, Ivet
中科院分区：
文献类型：
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作者：
Chennubhotla, Chakra;Yang, Zheng;Bahar, Ivet
尽管在理解变构通讯的分子基础方面做出了重大努力，但局部能量和构象变化在变构蛋白的三维结构中从配体结合位点协同扩散到远端区域的机制仍有待建立。最近的实验和理论证据支持这样一种观点，即生物分子的内在能力能够通过配体结合触发集体结构变化，从而促进变构通信。最近有两组研究证明了对这种内在的、结构诱导的效应提供了见解：弹性网络模型允许我们可视化最容易接近自然状态条件的构象的合作变化，以及信息理论方法，阐明了整体结构所青睐的最有效的信号传输途径。结合使用这两种方法，我们通过应用于细菌伴侣蛋白复合物GroEL-GroES的方式，强调了最合作的运动模式如何在介导变构信号的传播中发挥作用。在平衡条件下采样的全局动力学和网络拓扑固有的信号转导途径之间的功能耦合似乎控制了变构效应。
Despite significant efforts toward understanding the molecular basis of allosteric communication, the mechanisms by which local energetic and conformational changes cooperatively diffuse from ligand-binding sites to distal regions across the 3-dimensional structure of allosteric proteins remain to be established. Recent experimental and theoretical evidence supports the view that allosteric communication is facilitated by the intrinsic ability of the biomolecules to undergo collective changes in structure, triggered by ligand binding. Two groups of studies recently proved to provide insights into such intrinsic, structure-induced effects: elastic network models that permit us to visualize the cooperative changes in conformation that are most readily accessible near native state conditions, and information-theoretic approaches that elucidate the most efficient pathways of signal transmission favored by the overall architecture. Using a combination of these two approaches, we highlight, by way of application to the bacterial chaperonin complex GroEL-GroES, how the most cooperative modes of motion play a role in mediating the propagation of allosteric signals. A functional coupling between the global dynamics sampled under equilibrium conditions and the signal transduction pathways inherently favored by network topology appears to control allosteric effects.