Circadian rhythm signalling peptides and proteins articles from across Nature Portfolio

Cryptochromes are important components of biological clocks. Here, the authors uncover that a cryptochrome that enables synchronization of the reproduction of marine worms to the lunar cycle uses an inverse photo-oligomerization mechanism.

Metamorphic proteins can switch reversibly between two different native folds with entirely distinct functions, however, the triggers that induce the conformational switch remain largely underexplored. Here, the authors demonstrate the impact of a crowded environment on the switch of two metamorphic proteins KaiB and XCL1, and study the kinetics and thermodynamics of the switch using NMR spectroscopy.

Characterizing folding pathways of large proteins that bind complex cofactors is challenging. The authors use optical tweezers to study the 542-residue FAD-binding lightsensor protein dCRY, identifying several intermediates and cofactor binding steps, and dissecting the role of FAD moieties in folding.

Liu et al. demonstrate that CK2 phosphorylates CLOCK to promote its nuclear exportation and cytosolic accumulation, thereby acetylating and stabilizing PRPS1/2 and enhancing de novo nucleotide synthesis to facilitate liver tumour growth.

This work reveals the structural and biochemical basis for phosphorylation-dependent day/night signaling by KaiC in the cyanobacterial circadian clock.

Chandrasekaran et al. engineered the Drosophila circadian clock protein Cryptochrome (dCRY) to form the neutral semiquinone, which serves as a dark-state proxy. They find that the C-terminal tail of dCRY remains docked when the flavin ring is reduced but uncharged. dCRY His378 variants provide insights into the recognition motifs for dCRY turnover and strategies for optogenetic tools.

The molecular clock regulates the rhythmic transcription of myriad genes, leading to a circadian pattern of expression of the encoded proteins. A study demonstrates circadian regulation of expression of components of the protein secretory pathway, providing a mechanism to generate circadian patterns of secreted protein expression.

In mammals, a circadian timing system composed of a master clock in the brain’s suprachiasmatic nucleus and oscillators in peripheral organs drives daily rhythms of behavior and physiology. A study now reveals that the periodic oxidation of the CLOCK protein enhances the amplitude of cyclic gene expression and affects the daily rhythms of behavior.

The robustness of the circadian clock deteriorates with aging. Two new studies show that aging reprograms the circadian transcriptome in a cell-type-dependent manner and that such rewiring can be reversed by caloric restriction.