蛋白质降解中通过协同稳定性的温度补偿
Temperature compensation via cooperative stability in protein degradation
摘要：
温度补偿是昼夜节律振荡器的一个显著特性，表明振荡器系统的周期对温度变化不敏感;然而，其潜在机制仍不清楚。研究了蛋白质二聚化和蛋白质降解过程中的协同稳定性对两个振荡器温度补偿能力的影响。这里，协同稳定性意味着高阶低聚物比它们的单体对应物更稳定。振荡器的周期受动态系统的参数影响，而动态系统的参数又受温度影响。采用Repressilator和Atkinson振荡器分析了它们的周期温度敏感性。采用相位敏感性分析方法，分析了参数摄动对不同模型周期的影响。此外，我们利用其他研究提供的实验数据，以确定合理的参数温度灵敏度的范围。然后将线性规划方法应用于振荡系统，分析了蛋白质二聚化和协同稳定性对振荡周期温度敏感性的影响，反映了昼夜节律的温度补偿能力。我们的研究解释了生物钟的温度补偿机制。与非二聚体数学模型和线性蛋白质降解模型相比，我们的理论结果表明，协同稳定性引起的非线性蛋白质降解更有利于实现生物钟的温度补偿。
英文摘要：
Temperature compensation is a notable property of circadian oscillators that indicates the insensitivity of the oscillator system's period to temperature changes; the underlying mechanism, however, is still unclear. We investigated the influence of protein dimerization and cooperative stability in protein degradation on the temperature compensation ability of two oscillators. Here, cooperative stability means that high-order oligomers are more stable than their monomeric counterparts. The period of an oscillator is affected by the parameters of the dynamic system, which in turn are influenced by temperature. We adopted the Repressilator and the Atkinson oscillator to analyze the temperature sensitivity of their periods. Phase sensitivity analysis was employed to evaluate the period variations of different models induced by perturbations to the parameters. Furthermore, we used experimental data provided by other studies to determine the reasonable range of parameter temperature sensitivity. We then applied the linear programming method to the oscillatory systems to analyze the effects of protein dimerization and cooperative stability on the temperature sensitivity of their periods, which reflects the ability of temperature compensation in circadian rhythms. Our study explains the temperature compensation mechanism for circadian clocks. Compared with the no-dimer mathematical model and linear model for protein degradation, our theoretical results show that the nonlinear protein degradation caused by cooperative stability is more beneficial for realizing temperature compensation of the circadian clock.
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