Simulations of stressosome activation emphasize allosteric interactions between RsbR and RsbT.
Simulations of stressosome activation emphasize allosteric interactions between RsbR and RsbT.
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DOI：
10.1186/1752-0509-7-3
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发表时间：
2013-01-15
影响因子：
--
通讯作者：
Wolkenhauer O
中科院分区：
文献类型：
--
作者：
Liebal UW;Millat T;Marles-Wright J;Lewis RJ;Wolkenhauer O
应激体是一种细菌信号复合体，通过启动蛋白质伴侣转换级联反应环境变化，从而导致释放替代sigma因子σB。应激感知通过蛋白激酶RsbT增加应激小体传感器蛋白RsbR和支架蛋白RsbS的磷酸化。随后rbt与应激体的分离激活了σB级联。然而，在信号转导过程中，应激体中发生的物理事件的顺序尚不清楚。在这里，我们使用计算模型将应激小体的结构与应激激活后发生的磷酸化反应的效率联系起来。在我们的模型中，任何应激小体蛋白的磷酸化都依赖于它最近的邻居及其磷酸化状态。我们比较了关于应激体激活的不同假设，发现只有通过磷酸化RsbR来表征RsbT激酶变构激活的模型才能定性地再现实验数据。我们的模拟和对已发表数据的相关分析支持以下假设：(i)一个简单的布尔模型能够再现应激体动力学，（ii）不同的应激源诱导相同的应激体激活模式，我们也证实(i)磷酸化的RsbR激活RsbT， （ii） RsbX的主要目的是使RsbS-P去磷酸化。
The stressosome is a bacterial signalling complex that responds to environmental changes by initiating a protein partner switching cascade, which leads to the release of the alternative sigma factor, σB. Stress perception increases the phosphorylation of the stressosome sensor protein, RsbR, and the scaffold protein, RsbS, by the protein kinase, RsbT. Subsequent dissociation of RsbT from the stressosome activates the σB cascade. However, the sequence of physical events that occur in the stressosome during signal transduction is insufficiently understood. Here, we use computational modelling to correlate the structure of the stressosome with the efficiency of the phosphorylation reactions that occur upon activation by stress. In our model, the phosphorylation of any stressosome protein is dependent upon its nearest neighbours and their phosphorylation status. We compare different hypotheses about stressosome activation and find that only the model representing the allosteric activation of the kinase RsbT, by phosphorylated RsbR, qualitatively reproduces the experimental data. Our simulations and the associated analysis of published data support the following hypotheses: (i) a simple Boolean model is capable of reproducing stressosome dynamics, (ii) different stressors induce identical stressosome activation patterns, and we also confirm that (i) phosphorylated RsbR activates RsbT, and (ii) the main purpose of RsbX is to dephosphorylate RsbS-P.
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