Fig. 1.

The circadian cycle in KaiC phosphorylation and ATPase activity. Dephosphorylated KaiC (C) hexamers interact with KaiA (A), which stimulates autokinase activity. Initially, T432 is phosphorylated (magenta circles), and then S431 is phosphorylated (yellow circles). S431 phosphorylation permits KaiB (B) binding, which blocks the stimulation of KaiC autokinase activity; thereafter, KaiC dephosphorylates at T432 and then at S431. Throughout the cycle, the ATPase activity of KaiC is evident, although ATPase activity is higher (indicated by thicker lines) during the phase of autokinase activity. This ATPase activity is hypothesized to be translated into conformational changes in the KaiC hexamer (indicated by the progressive changes in color) that, in turn, affect ATPase activity. Not all KaiC monomers undergo phosphorylation or dephosphorylation in each cycle, although for simplicity here the cycle is diagrammed as if they do. However, monomer exchange with a free KaiC pool or among hexamers allows for synchronization among the population of KaiC hexamers and the maintenance of robust high-amplitude rhythms in ATPase activity and phosphorylation status. Input components (e.g., CikA and LdpA) and output components (e.g., SasA) also interact with the Kai complexes but are omitted for simplicity. (Modified from ref. 2.)