Published on Wed Sep 15 2021

Hidden conformations differentiate day and night in a circadian pacemaker

Swan, J., Sandate, C., Chavan, A., Freeberg, A., Etwaru, D., Ernst, D., Palacios, J., Golden, S., LiWang, A., Lander, G. C., Partch, C.

The AAA+ protein KaiC is the central pacemaker for cyanobacterial circadian rhythms. KaiC undergoes changes in autophosphorylation on its C-terminal (CII) domain that restrict binding of of clock proteins on its N-terminus to the evening.

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Abstract

The AAA+ protein KaiC is the central pacemaker for cyanobacterial circadian rhythms. Composed of two hexameric rings with tightly coupled activities, KaiC undergoes changes in autophosphorylation on its C-terminal (CII) domain that restrict binding of of clock proteins on its N-terminal (CI) domain to the evening. Here, we use cryo-electron microscopy to investigate how daytime and nighttime states of CII regulate KaiB binding to CI. We find that the CII hexamer is destabilized during the day but takes on a rigidified C2-symmetric state at night, concomitant with ring-ring compression. Residues at the CI-CII interface are required for phospho-dependent KaiB association, coupling ATPase activity on CI to cooperative KaiB recruitment. Together these studies reveal how daily changes in KaiC phosphorylation regulate cyanobacterial circadian rhythms.