Formaneck Mark S, Ma Liang, Cui Qiang
Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin, Madison, Wisconsin 53706, USA.
Proteins. 2006 Jun 1;63(4):846-67. doi: 10.1002/prot.20893.
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 beta4-alpha4 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 beta4-alpha4 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.
我们进行了32次10纳秒尺度的分子动力学模拟，以此探究细菌趋化性Y蛋白（CheY）中构象转变与磷酸化之间的耦合关系，CheY是蛋白质变构作用一个简单却具有代表性的例子。这些模拟结果支持了一种激活机制，即β4-α4环至少部分地控制着Tyr106的异构化。磷酸化作用和保守的Thr87的作用被认为是间接的，因为它们稳定了β4-α4环的活性构型。激活事件（磷酸化）和/或保守残基在稳定而非引发特定构象转变方面的间接作用，可能是许多信号系统的一个特征。目前对CheY的分析也有助于明确，蛋白质变构的“旧”观点（诱导契合）和“新”观点（群体转移）都不完整，因为它们分别强调了变构转变的动力学（机制）和热力学方面。在这方面，一个值得进一步分析的问题是，协同集体运动和顺序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时的相互作用。
