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

TL;DR

This paper explores how intrinsically disordered protein regions (IDRs) are crucial for the function and regulation of the eukaryotic circadian clock, acting as dynamic modules that support robust timing and output.

Contribution

It provides a comprehensive review of the biophysical mechanisms of IDRs and their roles in circadian proteins across diverse eukaryotic species.

Findings

IDRs are prevalent in core clock proteins from fungi to mammals.

IDRs facilitate dynamic interactions essential for circadian regulation.

IDRs contribute to the robustness and flexibility of the circadian clock.

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.