Eguchi Kohei, Yoda Mitsumasa, Terada Tomoki P, Sasai Masaki
Department of Computational Science and Engineering, Nagoya University, Nagoya 464-8603, Japan.
Biophys J. 2008 Aug;95(4):1773-84. doi: 10.1529/biophysj.107.127555. Epub 2008 May 23.
By incubating the mixture of three cyanobacterial proteins, KaiA, KaiB, and KaiC, with ATP in vitro, T. Kondo and his colleagues in recent work reconstituted the robust circadian rhythm of the phosphorylation level of KaiC. This finding indicates that protein-protein interactions and the associated hydrolysis of ATP suffice to generate the circadian rhythm. Several theoretical models have been proposed to explain the rhythm generated in this "protein-only" system, but the clear criterion to discern different possible mechanisms was not known. In this article, we discuss a model based on two basic assumptions: the assumption of the allosteric transition of a KaiC hexamer and the assumption of the monomer exchange between KaiC hexamers. The model shows a stable rhythmic oscillation of the phosphorylation level of KaiC, which is robust against changes in concentration of Kai proteins. We show that this robustness gives a clue to distinguish different possible mechanisms. We also discuss the robustness of oscillation against the change in the system size. Behaviors of the system with the cellular or subcellular size should shed light on the role of the protein-protein interactions in in vivo circadian oscillation.
通过在体外将三种蓝藻蛋白（KaiA、KaiB和KaiC）的混合物与ATP一起孵育，近藤滋及其同事在最近的研究中重建了KaiC磷酸化水平的稳健昼夜节律。这一发现表明，蛋白质-蛋白质相互作用以及相关的ATP水解足以产生昼夜节律。已经提出了几种理论模型来解释在这个“仅蛋白质”系统中产生的节律，但辨别不同可能机制的明确标准尚不清楚。在本文中，我们讨论了一个基于两个基本假设的模型：KaiC六聚体的变构转变假设和KaiC六聚体之间单体交换的假设。该模型显示了KaiC磷酸化水平的稳定节律振荡，对Kai蛋白浓度的变化具有稳健性。我们表明，这种稳健性为区分不同的可能机制提供了线索。我们还讨论了振荡对系统大小变化的稳健性。具有细胞或亚细胞大小的系统行为应有助于揭示蛋白质-蛋白质相互作用在体内昼夜振荡中的作用。
