Coupling of distant ATPase domains in the circadian clock protein KaiC

Nat Struct Mol Biol. 2022 Aug;29(8):759-766. doi: 10.1038/s41594-022-00803-w. Epub 2022 Jul 21.


The AAA+ family member KaiC is the central pacemaker for circadian rhythms in the cyanobacterium Synechococcus elongatus. Composed of two hexameric rings of adenosine triphosphatase (ATPase) domains with tightly coupled activities, KaiC undergoes a cycle of autophosphorylation and autodephosphorylation on its C-terminal (CII) domain that restricts binding of clock proteins on its N-terminal (CI) domain to the evening. Here, we use cryogenic-electron microscopy to investigate how daytime and nighttime states of CII regulate KaiB binding on CI. We find that the CII hexamer is destabilized during the day but takes on a rigidified C2-symmetric state at night, concomitant with ring-ring compression. Residues at the CI-CII interface are required for phospho-dependent KaiB association, coupling ATPase activity on CI to cooperative KaiB recruitment. Together, these studies clarify a key step in the regulation of cyanobacterial circadian rhythms by KaiC phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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


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