A cyanobacterial circadian clockwork.
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Cyanobacteria have become a major model system for analyzing circadian rhythms. The temporal program in this organism enhances fitness in rhythmic environments and is truly global--essentially all genes are regulated by the circadian system. The topology of the chromosome also oscillates and possibly regulates the rhythm of gene expression. The underlying circadian mechanism appears to consist of both a post-translational oscillator (PTO) and a transcriptional/translational feedback loop (TTFL). The PTO can be reconstituted in vitro with three purified proteins (KaiA, KaiB, and KaiC) and ATP. These three core oscillator proteins have been crystallized and structurally determined, the only full-length circadian proteins to be so characterized. The timing of cell division is gated by a circadian checkpoint, but the circadian pacemaker is not influenced by the status of the cell division cycle. This imperturbability may be due to the presence of the PTO that persists under conditions in which metabolism is repressed. Recent biochemical, biophysical, and structural discoveries have brought the cyanobacterial circadian system to the brink of explaining heretofore unexplainable biochemical characteristics of a circadian oscillator: the long time constant, precision, and temperature compensation. |
Structural Insights into a Circadian Oscillator
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An endogenous circadian system in cyanobacteria exerts pervasive control over cellular processes, including global gene expression. Indeed, the entire chromosome undergoes daily cycles of topological changes and compaction. The biochemical machinery underlying a circadian oscillator can be reconstituted in vitro with just three cyanobacterial proteins, KaiA, KaiB, and KaiC. These proteins interact to promote conformational changes and phosphorylation events that determine the phase of the in vitro oscillation. The high-resolution structures of these proteins suggest a ratcheting mechanism by which the KaiABC oscillator ticks unidirectionally. This posttranslational oscillator may interact with transcriptional and translational feedback loops to generate the emergent circadian behavior in vivo. The conjunction of structural, biophysical, and biochemical approaches to this system reveals molecular mechanisms of biological timekeeping. |
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