KaiC CII Ring Flexibility Governs the Rhythm of the Circadian Clock of Cyanobacteria

Abstract

The circadian clock orchestrates metabolism and cell division and imposes important consequences to health and diseases, such as obesity, diabetes, and cancer. It is well established that phosphorylation-dependent circadian rhythms are the result of circadian clock protein interactions, which regulate many intercellular processes according to time of day. The phosphorylation-dependent circadian rhythm undergoes a succession of phases: Phosphorylation Phase → Transition Phase → Dephosphorylation Phase. Each phase induces the next phase. However, the mechanism of each phase and how the phosphorylation and dephosphorylation phases are prevented from interfering with each other remain elusive. In this research, we used a newly developed isotopic labeling strategy in combination with a new type of nuclear magnetic resornance (NMR) experiment to obtain the structural and dynamic information of the cyanobacterial KaiABC oscillator system. This system is uniquely suited for the mechanistic studies: mixing KaiA, KaiB KaiC, and ATP generates a self-sustained ~24 h rhythm of KaiC phosphorylation in vitro. Our data strongly suggest that the dynamic states of KaiC underpin the timing mechanism of cyanobacterial oscillator.