Synchronization of circadian oscillation of phosphorylation level of KaiC in vitro.
In recent experimental reports, robust circadian oscillation of the phosphorylation level of KaiC has been reconstituted by incubating three cyanobacterial proteins, KaiA, KaiB, and KaiC, with ATP in vitro. This reconstitution indicates that protein-protein interactions and the associated ATP hydrolysis suffice to generate the oscillation, and suggests that the rhythm arising from this protein-based system is the circadian clock pacemaker in cyanobacteria. The mechanism of this reconstituted oscillation, however, remains elusive. In this study, we extend our previous model of oscillation by explicitly taking two phosphorylation sites of KaiC into account and we apply the extended model to the problem of synchrony of two oscillatory samples mixed at different phases. The agreement between the simulated and observed data suggests that the combined mechanism of the allosteric transition of KaiC hexamers and the monomer shuffling between them plays a key role in synchronization among KaiC hexamers and hence underlies the population-level oscillation of the ensemble of Kai proteins. The predicted synchronization patterns in mixtures of unequal amounts of two samples provide further opportunities to experimentally check the validity of the proposed mechanism. This mechanism of synchronization should be important in vivo for the persistent oscillation when Kai proteins are synthesized at random timing in cyanobacterial cells.
Department of Computational Science and Engineering, Nagoya University, Nagoya, Japan.
Tetsuro
T
Nagai
Tomoki P
TP
Terada
Masaki
M
Sasai
D000465:Algorithms; D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000378:metabolism*; D002940:Circadian Rhythm; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000378:metabolism*; D003198:Computer Simulation; D008954:Models, Biological; D010507:Periodicity; D010766:Phosphorylation; D055503:Protein Multimerization; D046940:Synechococcus / Q000502:physiology*
D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; C114271:KaiC protein, cyanobacteria