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Structural biology

The tick-tock of circadian clocks

Nature Reviews Microbiology volume 15, pages 256257 (2017) | Download Citation

Image: Philip Patenall/Macmillan Publishers Limited

Circadian clocks are cellular timekeeping systems that synchronize biological activities with night and day. In cyanobacteria, timekeeping is coordinated by a post-translational clock that consists of KaiA, KaiB and KaiC, which can tick autonomously in the presence of ATP through cyclical assembly into different forms. Now, two studies provide a structural basis to help us understand this periodic assembly.

Tseng, Goularte, Chavan et al. used crystallography and NMR to determine the structures of the KaiA, KaiB, and KaiC complexes and their output signalling proteins. These structures revealed that reversible transitions in the folding state of the metamorphic KaiB protein and oscillations of KaiC phosphorylation regulate the timing of signalling events, which, in turn, regulate the timing of gene expression.

In a second study, Snijder, Schuller et al. analysed native assemblies of the clock proteins by mass spectrometry and monitored numerous co-occurring Kai protein assembly stoichiometries. By freezing the clock in a single stoichiometry, the authors could determine its structure by hydrogen–deuterium exchange, cross-linking mass spectrometry and cryo-electron microscopy, which enabled the authors to propose a detailed model of the clock.

Together, these two studies provide insights into the structural basis for the dynamic assembly of clock proteins.


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    , , et al. Structural basis of the day–night transition in a bacterial circadian clock. Science 355, 1174–1180 (2017)

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    , et al. Structures of the cyanobacterial circadian oscillator frozen in a fully assembled state. Science 355, 1181–1184 (2017)

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