ArticleMolecular systems biology2020
Bayesian modeling reveals metabolite-dependent ultrasensitivity in the cyanobacterial circadian clock.
Article in Molecular systems biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Engineering TCR-controlled fuzzy logic into CAR T cells enhances therapeutic specificity.Cell · 2025Article
- A Compensated Clock: Temperature and Nutritional Compensation Mechanisms Across Circadian Systems.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The cyanobacterial circadian clock.Npj biological timing and sleep · 2025Review
- Review
- The inner workings of an ancient biological clock.Trends in biochemical sciences · 2024Review
- Nutritional compensation of the circadian clock is a conserved process influenced by gene expression regulation and mRNA stability.PLoS biology · 2023Article
- KidA, a multi-PAS domain protein, tunes the period of the cyanobacterial circadian oscillator.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Multimeric structure enables the acceleration of KaiB-KaiC complex formation induced by ADP/ATP exchange inhibition.PLoS computational biology · 2022Article
- Chaperones directly and efficiently disperse stress-triggered biomolecular condensates.Molecular cell · 2022Article
- Evolution of the repression mechanisms in circadian clocks.Genome biology · 2022Article
- Mechanism for the Generation of Robust Circadian Oscillations through Ultransensitivity and Differential Binding Affinity.The journal of physical chemistry. B · 2021Article
- Shift in Conformational Equilibrium Underlies the Oscillatory Phosphoryl Transfer Reaction in the Circadian Clock.Life (Basel, Switzerland) · 2021Article
- Bayesian modeling reveals metabolite-dependent ultrasensitivity in the cyanobacterial circadian clock.Molecular systems biology · 2020Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Mathematical models can enable a predictive understanding of mechanism in cell biology by quantitatively describing complex networks of interactions, but such models are often poorly constrained by available data. Owing to its relative biochemical simplicity, the core circadian oscillator in Synechococcus elongatus has become a prototypical system for studying how collective dynamics emerge from molecular interactions. The oscillator consists of only three proteins, KaiA, KaiB, and KaiC, and near-24-h cycles of KaiC phosphorylation can be reconstituted in vitro. Here, we formulate a molecularly detailed but mechanistically naive model of the KaiA-KaiC subsystem and fit it directly to experimental data within a Bayesian parameter estimation framework. Analysis of the fits consistently reveals an ultrasensitive response for KaiC phosphorylation as a function of KaiA concentration, which we confirm experimentally. This ultrasensitivity primarily results from the differential affinity of KaiA for competing nucleotide-bound states of KaiC. We argue that the ultrasensitive stimulus-response relation likely plays an important role in metabolic compensation by suppressing premature phosphorylation at nighttime.
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