  Biological oscillators are very diverse but can be classified based on
dynamical motifs such as the types of feedback loops present. The S. Elongatus
circadian clock is a remarkable phosphorylation-based oscillator that can be
reconstituted in vitro with only 3 different purified proteins: the clock
proteins KaiA, KaiB, and KaiC. Despite a growing body of knowledge about the
biochemistry of the Kai proteins, basic questions about how their interactions
lead to sustained oscillations remain unanswered. Here, we compare models of
this system that make opposing assumptions about whether KaiA sequestration
introduces a positive or a negative feedback loop. We find that the two
different feedback mechanisms can be distinguished experimentally by the
introduction of a protein that binds competitively with KaiA. Understanding the
dynamical mechanism responsible for oscillations in the Kai system may shed
light on the broader question of what clock architectures have been selected by
evolution and why.

Molecular Networks