A C2-symmetric state in the AAA+ KaiC hexamer coordinates structural and functional modes within a molecular clock

Cyanobacteria generate circadian rhythms via a molecular clock that keeps track of time post-translationally. At the center of this clock is the hexameric AAA+ protein KaiC, which undergoes a cycle of autophosphorylation in its C-terminal domain (CII) that governs binding of the other clock proteins, KaiA and KaiB, at its N-terminal domain (CI) over the course of the 24-hour day. KaiA promotes autophosphorylation by interacting with C-terminal loops of KaiC, known as A-loops, until KaiA is sequestered by KaiB, which cooperatively binds the CI domain during the evening.