Design principles of a conditional futile cycle exploited for regulation.
Design principles of a conditional futile cycle exploited for regulation.
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用于监管的条件无效循环的设计原则。
DOI：
10.1039/c5mb00055f
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发表时间：
2015
影响因子：
--
通讯作者：
Savageau,MichaelA
中科院分区：
文献类型：
--
作者：
Tolla,DeanA;Kiley,PatriciaJ;Lomnitz,JasonG;Savageau,MichaelA
在这份报告中，我们描述了无效循环的设计原则，作为环境传感器的调节蛋白提供快速适应。与代谢途径中避免的能量浪费的徒劳循环相反，在这里，我们描述了一种用于调节益处的有条件的徒劳循环。大肠杆菌的FNR（富马酸盐和硝酸盐还原）循环在两种情况下运行-在O2存在下的严格无效循环和缺氧条件下的途径。这里提出的计算结果使用FNR作为模型系统，并提供证据表明，这种转录因子及其不稳定的感觉辅因子之间的活动和非活动状态的循环提供快速的信号和适应。我们修改了以前开发的机械模型，以检查一个家庭的FNR模型，每个不同的循环速度，但在数学上受到限制，否则是等同的，我们确定了能量消耗和响应时间之间的权衡，可以通过进化来调整，以优化循环速率的FNR系统的特定生态环境。模拟模拟实验与建议的双突变株提供建议，实验测试我们的预测和识别潜在的健身效果。我们的方法提供了一个计算框架，用于分析其他有条件的无用循环，当将其置于更大的生物学背景中时，可能会发现其对生物体具有优势。
In this report, we characterize the design principles of futile cycling in providing rapid adaptation by regulatory proteins that act as environmental sensors. In contrast to the energetically wasteful futile cycles that are avoided in metabolic pathways, here we describe a conditional futile cycle exploited for a regulatory benefit. The FNR (fumarate and nitrate reduction) cycle in Escherichia coli operates under two regimes – a strictly futile cycle in the presence of O2 and as a pathway under anoxic conditions. The computational results presented here use FNR as a model system and provide evidence that cycling of this transcription factor and its labile sensory cofactor between active and inactive states affords rapid signaling and adaptation. We modify a previously developed mechanistic model to examine a family of FNR models each with different cycling speeds but mathematically constrained to be otherwise equivalent, and we identify a trade-off between energy expenditure and response time that can be tuned by evolution to optimize cycling rate of the FNR system for a particular ecological context. Simulations mimicking experiments with proposed double mutant strains offer suggestions for experimentally testing our predictions and identifying potential fitness effects. Our approach provides a computational framework for analyzing other conditional futile cycles, which when placed in their larger biological context may be found to confer advantages to the organism.