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Rhythmic ring-ring stacking drives the circadian oscillator clockwise.

Yong-Gang Chang1, Roger Tseng, Nai-Wei Kuo

  • 1School of Natural Sciences, University of California, Merced, CA 95343, USA.

Proceedings of the National Academy of Sciences of the United States of America
|September 13, 2012
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Cyanobacteria circadian clock proteins KaiA, KaiB, and KaiC form a rhythm. KaiC ring stacking exposes KaiB binding sites, driving clock transitions and regulating output via competition with SasA.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Systems Biology

Background:

  • Cyanobacteria utilize a circadian clock for temporal regulation.
  • The core oscillator involves KaiA, KaiB, and KaiC proteins, generating a ~24-hour phosphorylation rhythm of KaiC.
  • The precise mechanism driving this circadian rhythm has been unclear.

Purpose of the Study:

  • To elucidate the mechanism of the cyanobacterial circadian clock.
  • To identify how KaiC phosphorylation and dephosphorylation cycles are regulated.
  • To understand the role of protein-protein interactions in circadian rhythm generation.

Main Methods:

  • Investigated protein-protein interactions between KaiA, KaiB, and KaiC.
  • Utilized structural analysis to identify binding sites and conformational changes in KaiC.
  • Examined the effect of ADP on KaiC structure and protein binding.

Main Results:

  • KaiC ring stacking between CI and CII domains drives the switch between KaiC-KaiA (phosphorylation) and KaiC-KaiB (dephosphorylation) interactions.
  • The KaiB-binding site on the CI domain is exposed upon ring stacking.
  • KaiB competes with the clock output protein SasA for binding to the CI domain, suggesting regulation of clock output.
  • ADP binding can expose the KaiB-binding site independently of ring stacking, offering a clock resetting mechanism.

Conclusions:

  • KaiC ring stacking is a key mechanical driver of the cyanobacterial circadian clock.
  • The conformational changes in KaiC, regulated by ring stacking and ADP, control the cyclical activity of the oscillator.
  • This mechanism provides insights into circadian timekeeping and potential clock resetting strategies.