Structural mimicry confers robustness in the cyanobacterial circadian clock

Heisler, Joel; Swan, Jeffrey A.; Palacios, Joseph G.; Sancar, Cigdem; Ernst, Dustin C.; Spangler, Rebecca K.; Bagshaw, Clive R.; Tripathi, Sarvind; Crosby, Priya; Golden, Susan S.; Partch, Carrie L.; LiWang, Andy

doi:10.1101/2020.06.17.158394

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…We thus hypothesized that KidA PAS-ABC might bind selectively to fold-switched KaiB. To test this, we performed the same co-IP experiment using a mutant KaiB that is locked in the fold-switched form (fsKaiB-FLAG) to pull down KidA PAS-ABC ( 14 ). Much more KidA PAS-ABC was pulled down with fsKaiB-FLAG than with wtKaiB-FLAG, and protein complexes had fully formed after only a 30 min incubation ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…KaiA, KaiB, KaiB-FLAG, KaiC, and KaiC-EA proteins were purified as described previously ( 26 , 27 ). The fsKaiB-FLAG protein (KaiB-1–99-Y7A-I87A-Y93A-FLAG) was a gift from Andy LiWang ( 14 ). For KidA PAS-ABC purification, the KidA coding sequence for residues 1–359, preceded by the (PreScission Protease) PSP cleavage site (LFQ/GP) sequence and followed by the HA tag sequence, was cloned into the pRSET-B vector.…”

Section: Methodsmentioning

confidence: 99%

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KidA, a multi-PAS domain protein, tunes the period of the cyanobacterial circadian oscillator

Kim

Chi

Pattanayak

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The cyanobacterial clock presents a unique opportunity to understand the biochemical basis of circadian rhythms. The core oscillator, composed of the KaiA, KaiB, and KaiC proteins, has been extensively studied, but a complete picture of its connection to the physiology of the cell is lacking. To identify previously unknown components of the clock, we used KaiB locked in its active fold as bait in an immunoprecipitation/mass spectrometry approach. We found that the most abundant interactor, other than KaiC, was a putative diguanylate cyclase protein predicted to contain multiple Per-Arnt-Sim (PAS) domains, which we propose to name KidA. Here we show that KidA directly binds to the fold-switched active form of KaiB through its N-terminal PAS domains. We found that KidA shortens the period of the circadian clock both in vivo and in vitro and alters the ability of the clock to entrain to light-dark cycles. The dose-dependent effect of KidA on the clock period could be quantitatively recapitulated by a mathematical model in which KidA stabilizes the fold-switched form of KaiB, favoring rebinding to KaiC. Put together, our results show that the period and amplitude of the clock can be modulated by regulating the access of KaiB to the fold-switched form.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

KidA, a multi-PAS domain protein, tunes the period of the cyanobacterial circadian oscillator

Kim

Chi

Pattanayak

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…That being said, the mechanisms we discuss are far from a complete picture of circadian timekeeping. In fact, factors like co-operative binding or ultrasensitivity also play key roles [35,36].…”

Section: Discussionmentioning

confidence: 99%

Evolution of the repression mechanisms in circadian clocks

Tyler

Dunlap

et al. 2022

Genome Biol

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Background Circadian (daily) timekeeping is essential to the survival of many organisms. An integral part of all circadian timekeeping systems is negative feedback between an activator and repressor. However, the role of this feedback varies widely between lower and higher organisms. Results Here, we study repression mechanisms in the cyanobacterial and eukaryotic clocks through mathematical modeling and systems analysis. We find a common mathematical model that describes the mechanism by which organisms generate rhythms; however, transcription’s role in this has diverged. In cyanobacteria, protein sequestration and phosphorylation generate and regulate rhythms while transcription regulation keeps proteins in proper stoichiometric balance. Based on recent experimental work, we propose a repressor phospholock mechanism that models the negative feedback through transcription in clocks of higher organisms. Interestingly, this model, when coupled with activator phosphorylation, allows for oscillations over a wide range of protein stoichiometries, thereby reconciling the negative feedback mechanism in Neurospora with that in mammals and cyanobacteria. Conclusions Taken together, these results paint a picture of how circadian timekeeping may have evolved.

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“…Interestingly, KaiB is known to flip between an inactive (ground) and active (fold-switched) state [ 18 ], and the structural similarity between the fold-switched form of KaiB and N-terminal domain of SasA has previously been suggested [ 18 ], hinting at their competition for binding KaiC [ 51 , 53 ]. Although KaiC–SasA binding peaks before that of KaiC–KaiB, there is a significant overlap between those binding activities [ 54 ], and it is difficult to conclude what accounts for this difference between SasA’s and KaiB’s affinities to KaiC at this point [ 55 ].…”

Section: Physiological Rhythm Through the Output Pathwaymentioning

confidence: 99%

The Circadian Clock—A Molecular Tool for Survival in Cyanobacteria

Kim

Kaur

Jang

et al. 2020

Life

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Cyanobacteria are photosynthetic organisms that are known to be responsible for oxygenating Earth’s early atmosphere. Having evolved to ensure optimal survival in the periodic light/dark cycle on this planet, their genetic codes are packed with various tools, including a sophisticated biological timekeeping system. Among the cyanobacteria is Synechococcus elongatus PCC 7942, the simplest clock-harboring organism with a powerful genetic tool that enabled the identification of its intricate timekeeping mechanism. The three central oscillator proteins—KaiA, KaiB, and KaiC—drive the 24 h cyclic gene expression rhythm of cyanobacteria, and the “ticking” of the oscillator can be reconstituted inside a test tube just by mixing the three recombinant proteins with ATP and Mg2+. Along with its biochemical resilience, the post-translational rhythm of the oscillation can be reset through sensing oxidized quinone, a metabolite that becomes abundant at the onset of darkness. In addition, the output components pick up the information from the central oscillator, tuning the physiological and behavioral patterns and enabling the organism to better cope with the cyclic environmental conditions. In this review, we highlight our understanding of the cyanobacterial circadian clock and discuss how it functions as a molecular chronometer that readies the host for predictable changes in its surroundings.

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Structural mimicry confers robustness in the cyanobacterial circadian clock

Cited by 4 publications

References 33 publications

KidA, a multi-PAS domain protein, tunes the period of the cyanobacterial circadian oscillator

KidA, a multi-PAS domain protein, tunes the period of the cyanobacterial circadian oscillator

Evolution of the repression mechanisms in circadian clocks

The Circadian Clock—A Molecular Tool for Survival in Cyanobacteria

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