Structural basis of the day-night transition in a bacterial circadian clock

By R. Tseng, N. F. Goularte, Archana G. Chavan, J. Luu, S. Cohen, Yong-Gang Chang, Joel Heisler, Sheng Li, A. Michael, S. Tripathi and 3 more. 2017

169 citations recorded by the source corpus.

Molecular clockwork from cyanobacteria The cyanobacterial circadian clock oscillator can be reconstituted in a test tube from just three proteins—KaiA, KaiB, and KaiC—and adenosine triphosphate (ATP). Tseng et al. studied crystal and nuclear magnetic resonance structures of complexes of the oscillator proteins and their signaling output proteins and tested the in vivo effects of structure-based mutants. Large conformational changes in KaiB and ATP hydrolysis by KaiC are coordinated with binding to output protein, which couples signaling and the day-night transitions of the clock. Snijder et al. provide complementary analysis of the oscillator proteins by mass spectrometry and cryo–electron microscopy. Their results help to explain the structural basis for the dynamic assembly of the oscillator complexes. Science, this issue p. 1174, p. 1181 Cyanobacteria make a clock from just three proteins. Circadian clocks are ubiquitous timing systems that induce rhythms of biological activities in synchrony with night and day. In cyanobacteria, timing is generated by a posttranslational clock consisting of KaiA, KaiB, and KaiC proteins and a set of output signaling proteins, SasA and CikA, which transduce this rhythm to control gene expression. Here, we describe crystal and nuclear magnetic resonance structures of KaiB-KaiC,KaiA-KaiB-KaiC, and CikA-KaiB complexes. They reveal how the metamorphic properties of KaiB, a protein that adopts two distinct folds, and the post–adenosine triphosphate hydrolysis state of KaiC create a hub around which nighttime signaling events revolve, including inactivation of KaiA and reciprocal regulation of the mutually antagonistic signaling proteins, SasA and CikA.

Subfields: Cellular and Molecular Neuroscience, Endocrine and Autonomic Systems, Molecular Biology

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Citations in the corpus

Predicting multiple conformations via sequence clustering and AlphaFold2 (2023, neutral): “Finally, this was cross-checked with a full KaiC tree published previously 32 to ensure coverage across all phyla expected to contain KaiB-type proteins.”
From primordial clocks to circadian oscillators (2023, background): “In the canonical kaiABC system, the interaction between KaiB and KaiC is required to provide a new binding interface that sequesters KaiA from its activating binding site, thereby promoting autodephosphorylation at the optimum temperature of the organism 24–26 .”
Minimal tool set for a prokaryotic circadian clock (2016, background): “Two very recent studies provide a structural basis for the dynamic assembly of clock proteins by using crystallography and NMR [32], and mass spectrometry and cryo-electron microscopy of the native proteins [33].”
AlphaFold2 fails to predict protein fold switching (2022, background): “We define ground state in two ways: first as isolated protein when the other conformation binds a ligand, second as a preferred conformation suggested by the literature, such as the ground state tetrameric conformation of KaiB, 35 and third as one of two bound conformers (Table S5).”
Prediction of multiple conformational states by combining sequence clustering with AlphaFold2 (2022, background): “The thermodynamically favored state for KaiB from Thermosynechococcus elongatus (KaiB TE ) is the ground state; the FS structure was first solved in complex with KaiC 31 , and was solved for the isolated KaiB by introducing stabilizing mutations to this variant 31 .”
Extant fold-switching proteins are widespread (2018, background): “Currently, extant fold-switching proteins are thought to be rare (12), with reviews of the subject focusing on a handful of important examples (6, 9, 13, 14).”
AlphaDesign: A de novo protein design framework based on AlphaFold (2021, background): “…sequence space contains information about protein conformational change when interacting with other proteins, we predict the structures of two proteins known to have diﬀerent monomeric and oligomeric states – KaiB, a circadian clock protein [104] and amyloid-β involved in Alzheimer’s disease [105].”