Conformational changes in the negative arm of the circadian clock correlate with dynamic interactomes involved in post-transcriptional regulation

Pelham, Jacqueline F.; Mosier, Alexander E.; Altshuler, S. C.; Rhodes, Morgan L; Kirchhoff, C. L.; Fall, William; Mann, Catherine; Baik, Lisa; Chiu, Joanna C.; Hurley, Jennifer M.

doi:10.1016/j.celrep.2023.112376

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“…This cycle repeats every day, with a periodicity of 22.5 h under constant conditions. FRQ is an intrinsically disordered protein (IDP) ( 4 – 6 ) and is slowly and progressively phosphorylated throughout the day, modifying its structure and interactors. Several kinases and phosphatases are involved in the regulation of FRQ-WCC interaction and therefore, in determining the length of the circadian period ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Methylxanthines Modulate Circadian Period Length Independently of the Action of Phosphodiesterase

et al. 2023

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Section: Introductionmentioning

confidence: 99%

Methylxanthines Modulate Circadian Period Length Independently of the Action of Phosphodiesterase

et al. 2023

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Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator

Jankowski,

Griffith,

Shastry

et al. 2024

Nat Commun

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Organismal physiology is widely regulated by the molecular circadian clock, a feedback loop composed of protein complexes whose members are enriched in intrinsically disordered regions. These regions can mediate protein-protein interactions via SLiMs, but the contribution of these disordered regions to clock protein interactions had not been elucidated. To determine the functionality of these disordered regions, we applied a synthetic peptide microarray approach to the disordered clock protein FRQ in Neurospora crassa. We identified residues required for FRQ’s interaction with its partner protein FRH, the mutation of which demonstrated FRH is necessary for persistent clock oscillations but not repression of transcriptional activity. Additionally, the microarray demonstrated an enrichment of FRH binding to FRQ peptides with a net positive charge. We found that positively charged residues occurred in significant “blocks” within the amino acid sequence of FRQ and that ablation of one of these blocks affected both core clock timing and physiological clock output. Finally, we found positive charge clusters were a commonly shared molecular feature in repressive circadian clock proteins. Overall, our study suggests a mechanistic purpose for positive charge blocks and yielded insights into repressive arm protein roles in clock function.

show abstract

Conformational changes in the negative arm of the circadian clock correlate with dynamic interactomes involved in post-transcriptional regulation

Cited by 2 publications

References 119 publications

Methylxanthines Modulate Circadian Period Length Independently of the Action of Phosphodiesterase

Methylxanthines Modulate Circadian Period Length Independently of the Action of Phosphodiesterase

Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator

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