Closing the negative feedback loop: a tandem ATPase keeps circadian time by coupling distant enzymatic activities

The cyanobacterial circadian clock has served as an ideal model system to study the relationship between biomolecular kinetics and macroscopic biological timing. In this system, two domains of the hexameric AAA+ protein KaiC, termed CI and CII, have distinct biochemical activities whose relationship is key to creating a negative feedback loop that controls cyanobacterial rhythms. Together with two additional clock proteins, KaiA and KaiB, this system hydrolyzes ATP to generate autonomous rhythms that track circadian time in vivo.