page_title: Bacterial circadian rhythm
section_title: Visualizing the clockwork's "gears": structural biology of clock proteins
hierarchical_section_title: Bacterial circadian rhythm / Visualizing the clockwork's "gears": structural biology of clock proteins
caption_attribution_description: English: Clock Protein KaiC hexamer + 12 ATP (green), Synechococcus sp.
context_page_description: Bacterial circadian rhythms, like other circadian rhythms, are endogenous "biological clocks" that have the following three characteristics: in constant conditions they oscillate with a period that is close to, but not exactly, 24 hours in duration, this "free-running" rhythm is temperature compensated, and the rhythm will entrain to an appropriate environmental cycle.
  Until the mid-1980s, it was thought that only eukaryotic cells had circadian rhythms. It is now known that cyanobacteria have well-documented circadian rhythms that meet all the criteria of bona fide circadian rhythms. In these bacteria, three key proteins whose structures have been determined can form a molecular clockwork that orchestrates global gene expression. This system enhances the fitness of cyanobacteria in rhythmic environments.
context_section_description: The cyanobacterial circadian system is so far unique in that it is the only circadian system in which the structures of full-length clock proteins have been solved. In fact, the structures of all three of the Kai proteins have been determined. KaiC forms a hexamer that resembles a double doughnut with a central pore that is partially sealed at one end. There are twelve ATP-binding sites in KaiC and the residues that are phosphorylated during the in vitro phosphorylation rhythm have been identified. KaiA has two major domains and forms dimers in which the N-terminal domains are "swapped" with the C-terminal domains. KaiB has been successfully crystallized from three different species of cyanobacteria and forms dimers or tetramers.
  The three-dimensional structures have been helpful in elucidating the cyanobacterial clock mechanism by providing concrete models for the ways in which the three Kai proteins interact and influence each other. The structural approaches have also allowed the KaiA/KaiB/KaiC complexes to be visualized as a function of time, which enabled sophisticated mathematical modeling of the in vitro phosphorylation rhythm. Therefore, the cyanobacterial clock components and their interactions can be visualized in four dimensions (three in space, one in time).The temporal formation patterns of the KaiA/KaiB/KaiC complex have been elucidated, along with an interpretation of the core mechanism based on KaiC phosphorylation patterns and the dynamics of the KaiA/KaiB/KaiC complex. In addition, single-molecule methods (high-speed atomic force microscopy) have been applied to visualize in real time and quantify the dynamic interactions of KaiA with KaiC on sub-second timescales. These interactions regulate the circadian oscillation by modulating the magnesium binding in KaiC.
  An alternative view for the core mechanism of this remarkable clock is based on observations of the ATPase activity of KaiC. KaiC hydrolyses ATP at the remarkably slow rate of only 15 ATP molecules per KaiC monomer per 24 hours. The rate of this ATPase activity is temperature compensated, and the activities of wild-type and period-mutant KaiC proteins are directly proportional to their in vivo circadian frequencies, suggesting that the ATPase activity defines the circadian period. Therefore, some authors have proposed that the KaiC ATPase activity constitutes the most fundamental reaction underlying circadian periodicity in cyanobacteria.
caption: Clock Protein KaiC hexamer, Synechococcus sp.
exif: {}