Orderly wheels of the cyanobacterial clock

Rust, Michael J.

doi:10.1073/pnas.1214901109

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…In vitro, the system of KaiABC proteins undergoes sustained oscillations as evidenced by the phosphorylation state of the KaiC protein. These oscillations have been shown to have many of the same robust features as those observed in the circadian oscillations they support in cyanobacteria. , The KaiABC model system has been probed in many experimental and theoretical studies. , These have elucidated some of the necessary requirements for the generation of sustained oscillations. ,,− Despite these advances, understanding the biochemical and biophysical driving forces that are responsible for sustaining robust oscillations remains an open question. ,,,,, …”

Section: Introductionmentioning

confidence: 99%

Mechanism for the Generation of Robust Circadian Oscillations through Ultransensitivity and Differential Binding Affinity

2021

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Biochemical circadian rhythm oscillations play an important role in many signaling mechanisms. In this work, we explore some of the biophysical mechanisms responsible for sustaining robust oscillations by constructing a minimal but analytically tractable model of the circadian oscillations in the KaiABC protein system found in the cyanobacteria S. elongatus. In particular, our minimal model explicitly accounts for two experimentally characterized biophysical features of the KaiABC protein system, namely, a differential binding affinity and an ultrasensitive response. Our analytical work shows how these mechanisms might be crucial for promoting robust oscillations even in suboptimal nutrient conditions. Our analytical and numerical work also identifies mechanisms by which biological clocks can stably maintain a constant time period under a variety of nutrient conditions. Finally, our work also explores the thermodynamic costs associated with the generation of robust sustained oscillations and shows that the net rate of entropy production alone might not be a good figure of merit to asses the quality of oscillations.

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Section: Introductionmentioning

confidence: 99%

Mechanism for the Generation of Robust Circadian Oscillations through Ultransensitivity and Differential Binding Affinity

2021

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“…The best-studied example of biological posttranslational protein oscillators is the KaiABC system in cyanobacteria ( 8 ). By placing only the proteins KaiA, KaiB, and KaiC in a test tube, along with abundant adenosine triphosphate, the KaiC proteins collectively get sequentially phosphorylated and dephosphorylated, forming an oscillatory cycle ( 9 , 10 ). While the KaiC proteins generally exist in a hexameric state, monomers are shuffled among the hexamers during only a certain phase of the oscillatory cycle ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Self-assembly–based posttranslational protein oscillators

et al. 2020

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Recent advances in synthetic posttranslational protein circuits are substantially impacting the landscape of cellular engineering and offer several advantages compared to traditional gene circuits. However, engineering dynamic phenomena such as oscillations in protein-level circuits remains an outstanding challenge. Few examples of biological posttranslational oscillators are known, necessitating theoretical progress to determine realizable oscillators. We construct mathematical models for two posttranslational oscillators, using few components that interact only through reversible binding and phosphorylation/dephosphorylation reactions. Our designed oscillators rely on the self-assembly of two protein species into multimeric functional enzymes that respectively inhibit and enhance this self-assembly. We limit our analysis to within experimental constraints, finding (i) significant portions of the restricted parameter space yielding oscillations and (ii) that oscillation periods can be tuned by several orders of magnitude using recent advances in computational protein design. Our work paves the way for the rational design and realization of protein-based dynamic systems.

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“…The best-studied example of biological posttranslational protein oscillators is the KaiABC system in cyanobacteria [8]. By placing only the proteins KaiA, KaiB, and KaiC in a test tube, along with abundant ATP, the KaiC proteins collectively get sequentially phosphorylated and dephosphorylated, forming an oscillatory cycle [9,10]. While the KaiC proteins generally exist in a hexameric state, monomers are shuffled among the hexamers during only a certain phase of the oscillatory cycle [11].…”

Section: Introductionmentioning

confidence: 99%

Self-assembly based post-translational protein oscillators

Kimchi

Goodrich

Courbet

et al. 2020

Preprint

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Recent advances in synthetic post-translational protein circuits are significantly impacting the landscape of biomimicry engineering. However, designing sustained dynamic phenomena in these circuits remains an outstanding challenge. Inspired by the KaiABC system regulating the circadian clock in cyanobacteria, we develop two experimentally realizable post-translational oscillators. The oscillators rely on a small number of components interacting only through reversible binding and phosphorylation/dephosphorylation reactions.

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Orderly wheels of the cyanobacterial clock

Cited by 4 publications

References 19 publications

Mechanism for the Generation of Robust Circadian Oscillations through Ultransensitivity and Differential Binding Affinity

Mechanism for the Generation of Robust Circadian Oscillations through Ultransensitivity and Differential Binding Affinity

Self-assembly–based posttranslational protein oscillators

Self-assembly based post-translational protein oscillators

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