Mechanism of robust circadian oscillation of KaiC phosphorylation in vitro

TL;DR

This paper presents a model explaining the robust circadian oscillation of KaiC phosphorylation in vitro, emphasizing allosteric transitions and monomer exchange, and discusses how robustness can distinguish underlying mechanisms.

Contribution

The study introduces a new model based on allosteric transitions and monomer exchange that explains the robustness of KaiC phosphorylation oscillations in vitro.

Findings

The model exhibits stable rhythmic oscillations resistant to protein concentration changes.

Robustness of oscillation helps differentiate between possible underlying mechanisms.

System size influences oscillation robustness, providing insights into in vivo circadian regulation.

Abstract

By incubating the mixture of three cyanobacterial proteins, KaiA, KaiB, and KaiC, with ATP in vitro, Kondo and his colleagues reconstituted the robust circadian rhythm of the phosphorylation level of KaiC (Science, 308; 414-415 (2005)). 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 paper, we discuss a model based on the 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.