Regulation mechanisms of the dual ATPase in KaiC

Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2119627119. doi: 10.1073/pnas.2119627119. Epub 2022 May 4.


KaiC is a dual adenosine triphosphatase (ATPase), with one active site in its N-terminal domain and another in its C-terminal domain, that drives the circadian clock system of cyanobacteria through sophisticated coordination of the two sites. To elucidate the coordination mechanism, we studied the contribution of the dual-ATPase activities in the ring-shaped KaiC hexamer and these structural bases for activation and inactivation. At the N-terminal active site, a lytic water molecule is sequestered between the N-terminal domains, and its reactivity to adenosine triphosphate (ATP) is controlled by the quaternary structure of the N-terminal ring. The C-terminal ATPase activity is regulated mostly by water-incorporating voids between the C-terminal domains, and the size of these voids is sensitive to phosphoryl modification of S431. The up-regulatory effect on the N-terminal ATPase activity inversely correlates with the affinity of KaiC for KaiB, a clock protein constitutes the circadian oscillator together with KaiC and KaiA, and the complete dissociation of KaiB from KaiC requires KaiA-assisted activation of the dual ATPase. Delicate interactions between the N-terminal and C-terminal rings make it possible for the components of the dual ATPase to work together, thereby driving the assembly and disassembly cycle of KaiA and KaiB.

Keywords: ATPase; KaiC; circadian clock; cyanobacteria; structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Bacterial Proteins / metabolism
  • CLOCK Proteins / metabolism
  • Circadian Clocks*
  • Circadian Rhythm
  • Circadian Rhythm Signaling Peptides and Proteins / genetics
  • Circadian Rhythm Signaling Peptides and Proteins / metabolism
  • Cyanobacteria* / metabolism
  • Phosphorylation


  • Bacterial Proteins
  • Circadian Rhythm Signaling Peptides and Proteins
  • CLOCK Proteins
  • Adenosine Triphosphatases