Lego clocks: building a clock from parts

Abstract

A new finding opens up speculation that the molecular mechanism of circadian clocks in Synechococcus elongatus is composed of multiple oscillator systems (Kitayama and colleagues, this issue, pp. 1513-1521), as has been described in many eukaryotic clock model systems. However, an alternative intepretation is that the pacemaker mechanism-as previously suggested-lies primarily in the rate of ATP hydrolysis by the clock protein KaiC.

Figure 1.

The KaiC hexamer undergoes daily cycles of autophosphorylation (red spheres) and dephosphorylation. Autophosphorylation is stimulated by KaiA during the night; KaiB inhibits KaiA aund supports dephosphorylation of KaiC during the day. Hypophosphorylated KaiC promotes autophosphorylation of the histidine kinase, SasA, which transfers a phosphate to RpaA. Phosphorylated RpaA activates global transciption of genes. The Kai proteins also regulate transcription via daily compaction and decompaction of the cyanobacterial chromosome (dark-green ovals).

Figure 2.

Structure and function of KaiC. (Top) Schematic outline of the KaiC hexamer. The N-terminal (N) and C-terminal (C) domains of a KaiC subunit are indicated. Each domain has low intrinsic ATPase activity and the C-terminal domain has autokinase activity. S431 and T432 in the C-terminal domain are phosphorylated (red spheres) by the C-terminal ATPase of the adjacent KaiC subunit. (Bottom) The ATPase activity and the phosphorylation state of KaiC oscillate with a circadian period. The abundance peaks of nonphosphorylated and phosphorylated KaiC are indicated relative to the ATPase rhythm.