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Interactive features of proteins composing eukaryotic circadian clocks.

Brian R Crane1, Michael W Young

  • 1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853;

Annual Review of Biochemistry
|June 7, 2014
PubMed
Summary

This review details the molecular mechanisms of eukaryotic circadian clocks, focusing on the structural variations of PAS domains in clock proteins across species. It highlights how modifications and external cues dynamically regulate clock function.

Keywords:
PAS domaincircadian rhythmglycosylationmetabolismphosphorylationphotoentrainment

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Area of Science:

  • Molecular Biology
  • Chronobiology
  • Structural Biology

Background:

  • Eukaryotic circadian clocks are fundamental biological timekeepers.
  • Understanding their molecular mechanisms is crucial for various physiological processes.
  • Recent advances have significantly improved our knowledge of these complex systems.

Purpose of the Study:

  • To review recent advances in understanding the molecular mechanisms of eukaryotic circadian clocks.
  • To discuss the structural variations of key clock protein domains, particularly the PAS domain.
  • To explore the influence of posttranslational modifications and external cues on clock function.

Main Methods:

  • Review of existing literature on circadian clock research.
  • Analysis of structural data for core clock proteins in fungi, insects, and mammals.
  • Discussion of experimental findings on posttranslational modifications and external cue effects.

Main Results:

  • The PAS (Per/Arnt/Sim) domain exhibits significant structural variation, enabling diverse roles as transcriptional activators and repressors.
  • Posttranslational modifications and external cues like light dynamically alter the conformation and function of core clock components.
  • Novel interactions between clock proteins and partners involved in metabolic and developmental pathways have been identified.

Conclusions:

  • Conserved structural motifs and platforms are utilized and elaborated upon to create dynamic molecular interactions within the circadian clock.
  • The circadian clock functions as a highly integrated system with orchestrated changes in molecular structure, conformation, and interactions.
  • This dynamic regulation allows for precise timing and coupling with essential cellular processes.