The cyanobacterial circadian clock is generated by three Kai proteins in the presence of ATP and magnesium. This remarkable system can measure circadian time for days on end in a test tube in vitro. We are interested in studying this biological protein nanomachine to better understand the basic principles that help to establish the long timescale biochemistry of circadian rhythms.


KaiC is the central pacemaker of this clock, with tandem ATPase domains (CI and CII) that each assemble into hexameric rings connected by a flexible linker. Information about the time of day is regulated by phosphorylation of two residues in the CII domain and transmitted to the CI domain to control interactions with KaiA and KaiB (top).


Working with our collaborators, Andy LiWang (UC Merced) and Susan Golden (UCSD), we recently solved several high-resolution structures of Kai protein complexes to demonstrate how KaiB binds to KaiC at night to sequester KaiA (left). We are continuing to study this amazing post-translational oscillator using biochemistry, solution biophysics, and structural biological methods from x-ray crystallography to cryo-electron microscopy to understand the molecular basis for circadian timekeeping.