Reconciling the "old" and "new" views of protein allostery: A molecular simulation study of chemotaxis Y protein (CheY)
Reconciling the "old" and "new" views of protein allostery: A molecular simulation study of chemotaxis Y protein (CheY)
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DOI：
10.1002/prot.20893
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发表时间：
2006-06-01
影响因子：
2.9
通讯作者：
Cui, Qiang
中科院分区：
文献类型：
--
作者：
Formaneck, Mark S.;Ma, Liang;Cui, Qiang
结合 32 个 10 纳秒尺度的分子动力学模拟来探索构象之间的耦合。细菌趋化 Y 蛋白 (CheY) 中的转变和磷酸化，作为蛋白质变构的一个简单但具有代表性的例子。这些模拟的结果支持了一种激活机制，其中β 4-α 4 环至少部分地控制异构化。 Tyr106。磷酸化和保守的 Thr87 的作用被认为是间接的，因为它们稳定了 β 4-α 4 环的活性构型。激活事件（磷酸化）和/或保守残基在稳定而不是引起特定构象转变中的间接作用可能是许多信号系统中的一个特征。 CheY 目前的分析还有助于明确蛋白质变构的“旧”（诱导契合）和“新”（群体转变）观点都不完整，因为它们分别强调变构转变的动力学（机械）和热力学方面。在这方面，值得进一步分析的问题涉及协同集体运动和连续局部结构变化在调节生物分子中远距离位点之间的协同性方面的相互作用。
A combination of thirty-two 10-ns-scale molecular dynamics simulations were used to explore the coupling between conformational. transition and phosphorylation in the bacteria chemotaxis Y protein (CheY), as a simple but representative example of protein allostery. Results from these simulations support an activation mechanism in which the beta 4-alpha 4 loop, at least partially, gates the isomerization. of Tyr106. The roles of phosphorylation and the conserved Thr87 are deemed indirect in that they stabilize the active configuration of the beta 4-alpha 4 loop. The indirect role of the activation event (phosphorylation) and/or conserved residues in stabilizing, rather than causing, specific conformational transition is likely a feature in many signaling systems. The current analysis of CheY also helps to make clear that neither the "old" (induced fit) nor the "new" (population shift) views for protein allostery are complete, because they emphasize the kinetic (mechanistic) and thermodynamic aspects of allosteric transitions, respectively. In this regard, an issue that warrants further analysis concerns the interplay of concerted collective motion and sequential local structural changes in modulating cooperativity between distant sites in biomolecules.