Department of Computational Science and Engineering, Nagoya University, Nagoya, Japan.
PLoS One. 2007 May 2;2(5):e408. doi: 10.1371/journal.pone.0000408.
Circadian rhythms in living organisms have long been attributed solely to a transcription-translation loop comprising a negative or positive feedback. The rhythms in cyanobacteria are known to be modulated by kaiC, kaiA and kaiB genes. It was recently shown, however, that their product proteins KaiC, KaiA and KaiB are sufficient to reconstitute the circadian rhythm in the phosphorylation level of KaiC in vitro. It has since been unclear why such an oscillatory behavior can occur in the absence of the apparent transcription-translation feedback. In the meantime, it has been reported that the monomer exchange between KaiC hexamers occurs in a phosphorylation-dependent manner, which suggests that the monomer shuffling is also involved in the circadian rhythm (H. Kageyama et al., Mol. Cell, 23, 161 (2006)). To further clarify the role of the monomer shuffling, we have performed a computational modeling of interactions among Kai proteins assuming the allosteric transition of KaiC hexamer as well as the monomer shuffling. The results show that the existence of both monomer shuffling and allosteric transition can synchronize the phosphorylation level of the KaiC hexamers, and stabilizes its oscillation.
生物体的昼夜节律长期以来被归因于仅由转录-翻译环组成的负反馈或正反馈。蓝藻的节律被认为是由 kaiC、kaiA 和 kaiB 基因调节的。然而，最近表明，它们的产物蛋白 KaiC、KaiA 和 KaiB 足以在体外重建 KaiC 磷酸化水平的昼夜节律。此后，不清楚为什么在没有明显的转录-翻译反馈的情况下会出现这种振荡行为。与此同时，有报道称 KaiC 六聚体之间的单体交换以磷酸化依赖的方式发生，这表明单体交换也参与了昼夜节律（H. Kageyama 等人，Mol. Cell，23，161（2006））。为了进一步阐明单体交换的作用，我们假设 KaiC 六聚体的变构跃迁以及单体交换，对 Kai 蛋白之间的相互作用进行了计算建模。结果表明，单体交换和变构跃迁的存在可以使 KaiC 六聚体的磷酸化水平同步，并稳定其振荡。
