Monomer-Shuffling and Allosteric Transition in KaiC Circadian Oscillation

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Abstract
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.