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Effects of Stochastic Single-Molecule Reactions on Coherent Ensemble Oscillations in the KaiABC Circadian Clock
journal contribution
posted on 2019-01-10, 19:34 authored by Masaki SasaiHow
do many constituent molecules in a biochemical system synchronize,
giving rise to coherent system-level oscillations? One system that
is particularly suitable for use in studying this problem is a mixture
solution of three cyanobacterial proteins, KaiA, KaiB, and KaiC: the
phosphorylation level of KaiC shows stable oscillations with a period
of approximately 24 h when these three Kai proteins are incubated
with ATP in vitro. Here, we analyze the mechanism behind synchronization
in the KaiABC system theoretically by enhancing a model previously
developed by the present author. Our simulation results suggest that
positive feedback between stochastic ATP hydrolysis and the allosteric
structural transitions in KaiC molecules drives oscillations of individual
molecules and promotes synchronization of oscillations of many KaiC
molecules. Our simulations also show that the ATPase activity of KaiC
is correlated with the oscillation frequency of an ensemble of KaiC
molecules. These results suggest that stochastic ATP hydrolysis in
each KaiC molecule plays an important role in regulating the coherent
system-level oscillations. This property is robust against changes
in the binding and unbinding rate constants for KaiA to/from KaiC
or KaiB, but the oscillations are sensitive to the rate constants
of the KaiC phosphorylation and dephosphorylation reactions.