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Revealing circadian mechanisms of integration and resilience by visualizing clock proteins working in real time

Author

Listed:
  • Tetsuya Mori

    (Vanderbilt University)

  • Shogo Sugiyama

    (Kanazawa University)

  • Mark Byrne

    (Physics, and Engineering)

  • Carl Hirschie Johnson

    (Vanderbilt University
    Vanderbilt University School of Medicine)

  • Takayuki Uchihashi

    (Nagoya University)

  • Toshio Ando

    (Kanazawa University)

Abstract

The circadian clock proteins KaiA, KaiB, and KaiC reconstitute a remarkable circa-24 h oscillation of KaiC phosphorylation that persists for many days in vitro. Here we use high-speed atomic force microscopy (HS-AFM) to visualize in real time and quantify the dynamic interactions of KaiA with KaiC on sub-second timescales. KaiA transiently interacts with KaiC, thereby stimulating KaiC autokinase activity. As KaiC becomes progressively more phosphorylated, KaiA’s affinity for KaiC weakens, revealing a feedback of KaiC phosphostatus back onto the KaiA-binding events. These non-equilibrium interactions integrate high-frequency binding and unbinding events, thereby refining the period of the longer term oscillations. Moreover, this differential affinity phenomenon broadens the range of Kai protein stoichiometries that allow rhythmicity, explaining how the oscillation is resilient in an in vivo milieu that includes noise. Therefore, robustness of rhythmicity on a 24-h scale is explainable by molecular events occurring on a scale of sub-seconds.

Suggested Citation

  • Tetsuya Mori & Shogo Sugiyama & Mark Byrne & Carl Hirschie Johnson & Takayuki Uchihashi & Toshio Ando, 2018. "Revealing circadian mechanisms of integration and resilience by visualizing clock proteins working in real time," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05438-4
    DOI: 10.1038/s41467-018-05438-4
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    Cited by:

    1. Chongbin Zheng & Evelyn Tang, 2024. "A topological mechanism for robust and efficient global oscillations in biological networks," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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