The cyanobacterial circadian clock is generated by interactions between three Kai proteins in the presence of an energy source (ATP). This remarkable system can measure circadian time for days on end in a test tube in vitro. We are interested in learning how this biological nanomachine tells time to learn basic principles that help to establish the long timescale biochemistry of circadian rhythms.
KaiC is the central pacemaker of this clock, with two tandem ATPase domains (CI and CII) that each assemble into hexameric rings connected by a flexible linker. Information about the time of day is transmitted between KaiC rings to influence interactions with KaiA and KaiB.
Despite this relatively simple organization, the lack of high-resolution structures for intermediate states formed by Kai protein complexes has limited our understanding of this molecular clock. We are currently pursuing atomic resolution details of this clock with collaborators Andy LiWang (UC Merced), Susan Golden (UCSD) and Greg Hura (LBNL).