Atomic-scale origins of slowness in the cyanobacterial circadian clock

Abstract

Circadian clocks generate slow and ordered cellular dynamics but consist of fast-moving bio-macromolecules; consequently, the origins of the overall slowness remain unclear. We identified the adenosine triphosphate (ATP) catalytic region [adenosine triphosphatase (ATPase)] in the amino-terminal half of the clock protein KaiC as the minimal pacemaker that controls the in vivo frequency of the cyanobacterial clock. Crystal structures of the ATPase revealed that the slowness of this ATPase arises from sequestration of a lytic water molecule in an unfavorable position and coupling of ATP hydrolysis to a peptide isomerization with high activation energy. The slow ATPase is coupled with another ATPase catalyzing autodephosphorylation in the carboxyl-terminal half of KaiC, yielding the circadian response frequency of intermolecular interactions with other clock-related proteins that influences the transcription and translation cycle.

Circadian Oscillators: Around the Transcription–Translation Feedback Loop and on to Output

“…However, even absent the KaiABC-based PTO, the TTFL is capable of driving temperature-compensated rhythmic gene expression (albeit with a long 48 hr period length) of a substantial portion of the genome [89], suggesting that while the PTO is required for robustness and proper periodicity it may cooperate with the TTFL for output. Two recent analyses have tied the slow rate of ATP hydrolysis in the PTO to rates of structural changes in the Kai proteins, via a slow peptide isomerization in KaiC [90] and a slow and rare shift between folded states of KaiB that affects its ability both to capture KaiA (and thereby promote KaiC dephosphorylation) and to bind to and activate CikA, thereby influencing output [32]. …”

Structural basis of the day-night transition in a bacterial circadian clock

“…KaiC uses multiple enzymatic activities to act as the central circadian pacemaker (22). It has two homologous domains (CI and CII) that belong to the AAA+ ATPase (adenosine triphosphatase) family (23), with each domain associating into a hexameric ring (Fig.…”

Just-So Stories and Origin Myths: Phosphorylation and Structural Disorder in Circadian Clock Proteins

“…Cyanobacteria build a clock that can run in a test tube with just three proteins and two phosphorylation sites (Nakajima et al, 2005), and that advances through a wonderfully choreographed sequence of subtle and sometimes rare and transient structural changes that eventually lead back to just where they started (Abe et al, 2015), and that …”…”