Shift in conformational equilibrium underlies the oscillatory phosphoryl transfer reaction in the circadian clock

Pyonghwa Kim, Neha Thati, Shreya Peshori, Hye In Jang, Yong Ick Kim

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Oscillatory phosphorylation/dephosphorylation can be commonly found in a biological system as a means of signal transduction though its pivotal presence in the workings of circadian clocks has drawn significant interest: for example in a significant portion of the physiology of Syn-echococcus elongatus PCC 7942. The biological oscillatory reaction in the cyanobacterial circadian clock can be visualized through its reconstitution in a test tube by mixing three proteins—KaiA, KaiB and KaiC—with adenosine triphosphate and magnesium ions. Surprisingly, the oscillatory phosphorylation/dephosphorylation of the hexameric KaiC takes place spontaneously and almost indefinitely in a test tube as long as ATP is present. This autonomous post‐translational modification is tightly regulated by the conformational change of the C‐terminal peptide of KaiC called the “A-loop” between the exposed and the buried states, a process induced by the time‐course binding events of KaiA and KaiB to KaiC. There are three putative hydrogen‐bond forming residues of the A‐loop that are important for stabilizing its buried conformation. Substituting the residues with alanine enabled us to observe KaiB’s role in dephosphorylating hyperphosphorylated KaiC, independent of KaiA’s effect. We found a novel role of KaiB that its binding to KaiC induces the A‐loop toward its buried conformation, which in turn activates the autodephosphorylation of KaiC. In addition to its traditional role of sequestering KaiA, KaiB’s binding contributes to the robustness of cyclic KaiC phosphorylation by inhibiting it during the dephosphorylation phase, effectively shift-ing the equilibrium toward the correct phase of the clock.

Original languageEnglish (US)
Article number1058
Issue number10
StatePublished - Oct 2021

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • General Biochemistry, Genetics and Molecular Biology
  • Space and Planetary Science
  • Palaeontology


  • Circadian clock
  • Dephosphorylation
  • KaiB
  • Kinase
  • Phosphatase
  • Phosphorylation


Dive into the research topics of 'Shift in conformational equilibrium underlies the oscillatory phosphoryl transfer reaction in the circadian clock'. Together they form a unique fingerprint.

Cite this