A sequestration feedback determines dynamics and temperature entrainment of the KaiABC circadian clock.

A sequestration feedback determines dynamics and temperature entrainment of the KaiABC circadian clock.
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DOI:
10.1038/msb.2010.44
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发表时间:
2010-07-13
影响因子:
9.9
通讯作者:
Kollmann, Markus
Kollmann, Markus
中科院分区:
生物学1区
文献类型:
--
作者:
Brettschneider, Christian;Rose, Rebecca J.;Hertel, Stefanie;Axmann, Ilka M.;Heck, Albert J. R.;Kollmann, Markus

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蓝细菌Synechococcus elongatus的昼夜节律由三种蛋白质KaiA、KaiB和KaiC控制。在试管中,这些蛋白质形成各种化学计量的复合物,并且KaiC的平均磷酸化水平在ATP存在下表现出强大的昼夜节律振荡。使用数学建模,我们能够定量再现实验观察到的KaiABC发条在体外的磷酸化动力学。因此,我们通过KaiA失活确定了一个高度非线性的反馈回路,作为KaiC磷酸化的关键同步机制。通过使用天然质谱的新方法,我们证实了理论上预测的复合物形成动力学,并表明KaiA的失活是KaiC六聚体和KaiBC复合物螯合的结果。为了进一步测试数学模型的预测能力,我们再现了所观察到的相同步动力学夹带温度循环。我们的模型给出了强有力的证据,基本的夹带机制产生的KaiAC和KaiBC复合物的丰度的温度依赖性变化。
The circadian rhythm of the cyanobacterium Synechococcus elongatus is controlled by three proteins, KaiA, KaiB, and KaiC. In a test tube, these proteins form complexes of various stoichiometry and the average phosphorylation level of KaiC exhibits robust circadian oscillations in the presence of ATP. Using mathematical modeling, we were able to reproduce quantitatively the experimentally observed phosphorylation dynamics of the KaiABC clockwork in vitro. We thereby identified a highly non-linear feedback loop through KaiA inactivation as the key synchronization mechanism of KaiC phosphorylation. By using the novel method of native mass spectrometry, we confirm the theoretically predicted complex formation dynamics and show that inactivation of KaiA is a consequence of sequestration by KaiC hexamers and KaiBC complexes. To test further the predictive power of the mathematical model, we reproduced the observed phase synchronization dynamics on entrainment by temperature cycles. Our model gives strong evidence that the underlying entrainment mechanism arises from a temperature-dependent change in the abundance of KaiAC and KaiBC complexes.
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