QUANTITATIVE BIOLOGY SEMINAR | Structural Gymnastics by Proteins Make the Clock Mechanism Go Around

Endogenous clocks regulate metabolism, physiology and behavior of most organisms in anticipation of daily swings in ambient light and temperature by synchronizing them to a ~24-h biochemical rhythm. Here, we will show in a model system that structural gymnastics by proteins make the clock mechanism go around. The “gears” of the cyanobacterial clock are composed of three proteins, KaiA, KaiB, and KaiC. Remarkably, when they are mixed together in a test tube with ATP, they generate a circadian rhythm of (auto)phosphorylation and (auto)dephosphorylation of the KaiC protein for many days. KaiA stimulates KaiC phosphorylation, whereas KaiB antagonizes KaiA to promote KaiC dephosphorylation. The field has been attempting to crack the mechanism using published crystal structures to model complexes of these proteins. However, we will show that surprisingly large conformational changes (not captured in the crystal structures) determine when and how the KaiABC complexes assemble and disassemble, setting up time steps in the clock.