Meshing the gears of the cyanobacterial circadian clock
- Center for Research on Biological Clocks, Department of Biology, Texas A&M University, College Station, TX 77843-3258
Aphysiological black box is to a biologist what an ornately decorated package is to a small child: a mysterious treasure that promises delightful toys within. With fitting élan, a small community of scientists has ripped open the packaging of the cyanobacterial circadian clock, compiled the parts list, examined the gears, and begun to piece together the mechanism. Over the past 2 years, the 3D molecular structures have been solved for the core components of the cyanobacterial circadian clock: KaiA, KaiB, and KaiC (1–6). In a surprisingly literal analogy to mechanical timepieces, the protein that seems to be at the heart of the clock mechanism, KaiC, forms a hexameric ring that even looks like a cog: the escape wheel, perhaps (5, 7, 8). Previous work has shown that KaiC has an autophosphorylation activity, and that the presence of KaiA and KaiB modulates the extent to which KaiC is phosphorylated (6, 9). In this issue of PNAS, Nishiwaki et al. (10) biochemically identify two amino acid residues on KaiC to which phosphoryl groups covalently attach, and show the necessity in vivo of a phosphorylation-competent residue at these positions. By searching the crystal structure for evidence of phosphorylated sites, Xu et al. (11) pinpoint a third residue that may “borrow” the phosphoryl group dynamically. Together, their work contributes richly to our understanding of what makes the gears mesh and turn to crank out a 24-h timing circuit.
The emerging model of the cyanobacterial circadian oscillator differs markedly from those that have been proposed for various eukaryotic systems (12, 13). In the latter schemes, many of the central components are either transcription factors that directly stimulate the …
