Robust and tunable circadian rhythms from differentially sensitive catalytic domains
Robust and tunable circadian rhythms from differentially sensitive catalytic domains
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DOI：
10.1073/pnas.1212113110
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发表时间：
2013-01-15
影响因子：
11.1
通讯作者：
Rust, Michael J.
中科院分区：
文献类型：
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作者：
Phong, Connie;Markson, Joseph S.;Rust, Michael J.
生物钟是一种无处不在的生物振荡器，它使生物体的行为与外部环境的日常循环相协调。为了确保与环境同步，即使输入信号改变幅度和相位，时钟的周期也必须保持在24小时左右。我们发现，在一个重建的昼夜节律系统，从蓝藻，这些相互冲突的要求是由中央时钟蛋白KaiC的两个域的不同功能得到满足：C-末端自激酶结构域通过ATP/ADP比集成输入信号，和缓慢的N-末端ATP酶作为一个独立的输入计时器。我们发现，在C-末端结构域的磷酸化，然后在N-末端结构域的ATP酶循环是必需的，以形成抑制性KaiB中心点KaiC复合物，驱动时钟的动态。我们提出了一个数学模型，在该模型中，ATP酶介导的负反馈延迟产生了一种补偿机制，该机制允许可调的相位和振幅，同时确保稳健的昼夜节律周期。
Circadian clocks are ubiquitous biological oscillators that coordinate an organism's behavior with the daily cycling of the external environment. To ensure synchronization with the environment, the period of the clock must be maintained near 24 h even as amplitude and phase are altered by input signaling. We show that, in a reconstituted circadian system from cyanobacteria, these conflicting requirements are satisfied by distinct functions for two domains of the central clock protein KaiC: the C-terminal autokinase domain integrates input signals through the ATP/ADP ratio, and the slow N-terminal ATPase acts as an input-independent timer. We find that phosphorylation in the C-terminal domain followed by an ATPase cycle in the N-terminal domain is required to form the inhibitory KaiB center dot KaiC complexes that drive the dynamics of the clock. We present a mathematical model in which this ATPase-mediated delay in negative feedback gives rise to a compensatory mechanism that allows a tunable phase and amplitude while ensuring a robust circadian period.