Orchestration of Circadian Timing by Macromolecular Protein Assemblies

Genetically encoded biological clocks are found broadly throughout eukaryotes and in cyanobacteria, where they generate circadian (about a day) rhythms that allow organisms to anticipate regular environmental changes and align their physiology and behavior with Earth's daily light/dark cycle. In recent years, many have sought to expand our biochemical and structural understanding of the clock proteins that constitute the molecular “cogs” of these biological clocks. These new studies are beginning to reveal how macromolecular assemblies of dedicated clock proteins form and evolve to contribute to the generation of clocks that function over the timescale of a day. This review will highlight structural and biochemical studies that provide important insight into the molecular mechanisms of cyanobacterial and vertebrate animal clocks. Collectively, these studies demonstrate emerging biochemical properties that appear to be shared by these different clocks, suggesting that there may be some conservation in the regulation and assembly of circadian macromolecular assemblies. [Display omitted] •Most clocks rely on transcriptional cycles, but some can occur posttranslationally.•Some biochemical principles may be shared by all clocks.•Clocks rely on the remodeling of core clock protein complexes throughout the day.•Slow biochemical or enzymatic steps are crucial for timekeeping in all clock types.•Clocks depend on competition for mutually exclusive binding at key interfaces.