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-Structure paper
Title | From primordial clocks to circadian oscillators. |
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Journal, issue, pages | Nature, Vol. 616, Issue 7955, Page 183-189, Year 2023 |
Publish date | Mar 22, 2023 |
Authors | Warintra Pitsawong / Ricardo A P Pádua / Timothy Grant / Marc Hoemberger / Renee Otten / Niels Bradshaw / Nikolaus Grigorieff / Dorothee Kern / |
PubMed Abstract | Circadian rhythms play an essential part in many biological processes, and only three prokaryotic proteins are required to constitute a true post-translational circadian oscillator. The evolutionary ...Circadian rhythms play an essential part in many biological processes, and only three prokaryotic proteins are required to constitute a true post-translational circadian oscillator. The evolutionary history of the three Kai proteins indicates that KaiC is the oldest member and a central component of the clock. Subsequent additions of KaiB and KaiA regulate the phosphorylation state of KaiC for time synchronization. The canonical KaiABC system in cyanobacteria is well understood, but little is known about more ancient systems that only possess KaiBC. However, there are reports that they might exhibit a basic, hourglass-like timekeeping mechanism. Here we investigate the primordial circadian clock in Rhodobacter sphaeroides, which contains only KaiBC, to elucidate its inner workings despite missing KaiA. Using a combination of X-ray crystallography and cryogenic electron microscopy, we find a new dodecameric fold for KaiC, in which two hexamers are held together by a coiled-coil bundle of 12 helices. This interaction is formed by the carboxy-terminal extension of KaiC and serves as an ancient regulatory moiety that is later superseded by KaiA. A coiled-coil register shift between daytime and night-time conformations is connected to phosphorylation sites through a long-range allosteric network that spans over 140 Å. Our kinetic data identify the difference in the ATP-to-ADP ratio between day and night as the environmental cue that drives the clock. They also unravel mechanistic details that shed light on the evolution of self-sustained oscillators. |
External links | Nature / PubMed:36949197 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.7 - 3.5 Å |
Structure data | EMDB-29505, PDB-8fwi: EMDB-29506, PDB-8fwj: EMDB-29507: Structure of dodecameric KaiC-RS-S413E/S414E - single hexamer focus map EMDB-29508: Structure of dodecameric KaiC-RS-S413E/S414E with bound KaiB-RS - single hexamer focus map EMDB-29509: KaiC-RS-S413E/S414E full dodecamer reconstruction EMDB-29510: KaiC-RS-S413E/S414E with bound KaiB-RS full dodecamer reconstruction PDB-8db3: PDB-8dba: |
Chemicals | ChemComp-ADP: ChemComp-MG: ChemComp-HOH: ChemComp-ATP: |
Source |
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Keywords | CIRCADIAN CLOCK PROTEIN / autokinase |