Disordered But Rhythmic: the role of intrinsic protein disorder in eukaryotic circadian timing

2025/08/25 by Usher, Emery T., Pelham, Jacqueline F.
#Biomolecules (q-bio.BM) #FOS: Biological sciences

paper · doi:10.48550/arxiv.2508.18493

Abstract

Intrinsically disordered protein regions (IDRs) are found across all domains of life and are characterized by a lack of stable 3D structure. Nevertheless, IDRs play critical roles in the most tightly regulated cellular processes, including in the core circadian clock. The molecular oscillator at the heart of circadian regulation leverages IDRs as dynamic interaction modules for activation and repression to support robust timekeeping and expand clock output and regulation. Here, we cover the biophysical mechanisms conferred by IDRs and their modulators. We survey the intrinsically disordered regions in clock proteins that are widely prevalent from fungi to mammals and discuss the importance of IDRs to the core clock and beyond.

Citations

• The SIK3-N783Y mutation is associated with the human natural short sleep trait
• Alternative splicing of Clock transcript mediates the response of circadian clocks to temperature changes
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• Circadian regulation of sunflower heliotropism, floral orientation, and pollinator visits
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