Computational studies of the principle of dynamic-change-driven protein interactions
Computational studies of the principle of dynamic-change-driven protein interactions
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DOI：
10.1016/j.str.2022.03.008
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发表时间：
2022-06-02
期刊：
影响因子：
5.7
通讯作者：
Buck, Matthias
中科院分区：
文献类型：
--
作者：
Li, Zhen-Lu;Mattos, Carla;Buck, Matthias
动态变构强调熵变的作用，表现为蛋白质波动的唯一变化而没有结构变化。这种熵驱动效应在很大程度上仍未得到充分研究。最重要的例子涉及蛋白质-配体相互作用，而对于信号传导和其他细胞事件至关重要的蛋白质-蛋白质相互作用在很大程度上尚未被探索。在这里，我们研究了蛋白质-蛋白质相互作用（Ras 与效应蛋白 Raf 的 Ras 结合域 [RBD] 结合）如何通过动态变构淬灭 Ras 内部运动来影响后续蛋白质关联过程（Ras 二聚化）的示例。我们还分别研究了点突变或环境温度对腺苷酸激酶 (ADK) 和 EphA2 SAM:Ship2 SAM 复合体中两个其他系统的蛋白质动力学和相互作用的影响。基于这些例子，我们假设动态变化驱动的蛋白质相互作用有不同的表现方式，并且它可能是一种普遍的生物现象。
Dynamic allostery emphasizes a role of entropy change manifested as a sole change in protein fluctuations without structural changes. This kind of entropy-driven effect remains largely understudied. The most significant examples involve protein-ligand interactions, leaving protein-protein interactions, which are critical in signaling and other cellular events, largely unexplored. Here we study an example of how protein-protein interaction (binding of Ras to the Ras binding domain [RBD] of the effector protein Raf) affects a subsequent protein association process (Ras dimerization) by quenching Ras internal motions through dynamic allostery. We also investigate the influence of point mutations or ambient temperature, respectively, on the protein dynamics and interaction of two other systems: in adenylate kinase (ADK) and in the EphA2 SAM:Ship2 SAM complex. Based on these examples, we postulate that there are different ways in which dynamic-change driven protein interactions are manifested and that it is likely a general biological phenomenon.