A Protein Fold Switch Joins the Circadian Oscillator to Clock Output in Cyanobacteria
By Yong-Gang Chang, S. Cohen, Connie Phong, W. Myers, Yong-Ick Kim, R. Tseng, Jenny J. Lin, Li Zhang, J. S. Boyd, Yvonne M Lee and 7 more. 2015
201 citations recorded by the source corpus.
Biochemical basis of a 24-hour clock Circadian clocks keep organisms in synch with such daily cycles as illumination, activity, and food availability. The circadian clock in cyanobacteria has the necessary 24-hour period despite its three component proteins having biochemical activities that occur on a much faster time scale. Abe et al. focused on the cyanobacterial clock component KaiC, an adenosine triphosphatase (ATPase) that can autophosphorylate and autodephosphorylate. The slow ATPase activity of KaiC, which is linked to a peptide isomerisation, provided the slow kinetics that set the speed of the 24-hour clock. Chang et al. found that another clock component, KaiB, also has slow changes in its protein conformation that help to set the oscillation period of the clock and its signaling output. Science, this issue pp. 312 and 324 Slow conformational change of a protein helps set the pace of a circadian clock. Organisms are adapted to the relentless cycles of day and night, because they evolved timekeeping systems called circadian clocks, which regulate biological activities with ~24-hour rhythms. The clock of cyanobacteria is driven by a three-protein oscillator composed of KaiA, KaiB, and KaiC, which together generate a circadian rhythm of KaiC phosphorylation. We show that KaiB flips between two distinct three-dimensional folds, and its rare transition to an active state provides a time delay that is required to match the timing of the oscillator to that of Earth’s rotation. Once KaiB switches folds, it binds phosphorylated KaiC and captures KaiA, which initiates a phase transition of the circadian cycle, and it regulates components of the clock-output pathway, which provides the link that joins the timekeeping and signaling functions of the oscillator.
Subfields: Cellular and Molecular Neuroscience, Endocrine and Autonomic Systems, Plant Science
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In Cellular and Molecular Neuroscience
Citations in the corpus
- Predicting multiple conformations via sequence clustering and AlphaFold2 (2023, positive): “Using this method, named AF-Cluster, we investigated the evolutionary distribution of predicted structures for the metamorphic protein KaiB 5 and found that predictions of both conformations were distributed in clusters across the KaiB family.”
- Extant fold-switching proteins are widespread (2018, background): “The slow interconversion between these two conformations helps to coordinate the cyanobacterial clock with the timing of the earth’s rotation (16).”
- Chronotype and Health Outcomes (2015, methodology): “Record of rectal temperature is the golden standard method 206 Curr Sleep Medicine Rep (2015) 1:205–211”
- Reversible fold-switching controls the functional cycle of the antitermination factor RfaH (2019, background): “coli BL21 (λ DE3) cells harboring plasmid pET11a_EcNusG-NTD(1-124), which encodes E.”
- Minimal tool set for a prokaryotic circadian clock (2016, background): “Residues K57, G88 and D90, which were suggested to regulate fold switching of KaiB-7942 [139], are the most prominent residues at the mentioned positions in KaiB1 proteins, but not highly conserved (Additional file 1: Figure S3).”