Structure and function from the circadian clock protein KaiA of
            <i>Synechococcus elongatus</i>
            : A potential clock input mechanism

Williams, Stanly B.; Vakonakis, Ioannis; Golden, Susan S.; LiWang, Andy

doi:10.1073/pnas.232517099

Cited by 190 publications

(253 citation statements)

References 38 publications

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“…Thus, ATP is a necessary cofactor for KaiC hexamerization. In the presence of ATP, KaiC is phosphorylated by KaiC itself, and the phosphorylation is enhanced by KaiA (7)(8)(9)(10). We demonstrated that two molecules of KaiA dimer can interact with one molecule of KaiC hexamer and that one molecule of KaiA dimer interacting with one molecule of KaiC hexamer is enough to enhance KaiC phosphorylation (5).…”

mentioning

confidence: 82%

Roles of Two ATPase-Motif-containing Domains in Cyanobacterial Circadian Clock Protein KaiC

Hayashi

Itoh

Uzumaki

et al. 2004

Journal of Biological Chemistry

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Cyanobacterial clock protein KaiC has a hexagonal, pot-shaped structure composed of six identical dumbbell-shaped subunits. Each subunit has duplicated domains, and each domain has a set of ATPase motifs. The two spherical regions of the dumbbell are likely to correspond to two domains. We examined the role of the two sets of ATPase motifs by analyzing the in vitro activity of ATP␥S binding, AMPPNP-induced hexamerization, thermostability, and phosphorylation of KaiC and by in vivo rhythm assays both in wild type KaiC (KaiC WT ) and KaiCs carrying mutations in either Walker motif A or deduced catalytic Glu residues. We demonstrated that 1) the KaiC subunit had two types of ATPbinding sites, a high affinity site in N-terminal ATPase motifs and a low affinity site in C-terminal ATPase motifs, 2) the N-terminal motifs were responsible for hexamerization, and 3) the C-terminal motifs were responsible for both stabilization and phosphorylation of the KaiC hexamer. We proposed the following reaction mechanism. ATP preferentially binds to the N-terminal high affinity site, inducing the hexamerization of KaiC. Additional ATP then binds to the C-terminal low affinity site, stabilizing and phosphorylating the hexamer. We discussed the effect of these KaiC mutations on circadian bioluminescence rhythm in cells of cyanobacteria.Circadian rhythms, 24-h biological oscillations of metabolic and behavioral activities observed ubiquitously in prokaryotes and eukaryotes, are endogenously regulated by circadian clocks. Several clock and clock-related genes from Drosophila, Neurospora, Arabidopsis, mice, and cyanobacteria have been cloned and analyzed (1).Cyanobacteria are the simplest organisms that exhibit circadian rhythms. We previously cloned and analyzed the kaiABC circadian clock gene cluster in the cyanobacterium Synechococcus sp. strain PCC 7942 (hereafter called Synechococcus) that is essential for the generation of circadian rhythms in cyanobacteria. The gene cluster consists of two

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confidence: 82%

Roles of Two ATPase-Motif-containing Domains in Cyanobacterial Circadian Clock Protein KaiC

Hayashi

Itoh

Uzumaki

et al. 2004

Journal of Biological Chemistry

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“…In one of the more remarkable discoveries in the field in recent years, it was shown that a circadian oscillation of KaiC phosphorylation could be reconstituted in vitro with the purified KaiA, KaiB, and KaiC proteins . KaiA enhances KaiC autophosphorylation, while KaiB antagonizes the effects of KaiA (Iwasaki et al, 2002;Williams et al, 2002;Kitayama et al, 2003;Xu et al, 2003).…”

Section: The Circadian Clock System In Cyanobacteriamentioning

confidence: 99%

No Promoter Left Behind: Global Circadian Gene Expression in Cyanobacteria

Woelfle

Johnson

2006

J Biol Rhythms

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Prokaryotic cyanobacteria express robust circadian (daily) rhythms under the control of a clock system that appears to be similar to those of eukaryotes in many ways. On the other hand, the KaiABC-based core cyanobacterial clockwork is clearly different from the transcriptiontranslation feedback loop model of eukaryotic clocks in that the cyanobacterial clock system regulates gene expression patterns globally, and specific clock gene promoters are not essential in mediating the circadian feedback loop. A novel model, the oscilloid model, proposes that the KaiABC oscillator ultimately mediates rhythmic changes in the status of the cyanobacterial chromosome, and these topological changes underlie the global rhythms of transcription. The authors suggest that this model represents one of several possible modes of regulating gene expression by circadian clocks, even those of eukaryotes. Keywords circadian; biological clock; kai; prokaryote; global gene expression; supercoiling Animals, plants, fungi, and cyanobacteria all display daily or circadian rhythms in their biochemistry, physiology, and/or behavior that are controlled by biological clocks (Dunlap et al., 2004). A variety of biological processes in various organisms are controlled by biological clocks such as gene expression, photosynthesis, sleeping/waking, and development, and this regulation is thought to help organisms adapt to the daily changes in light, temperature, and other factors in their environment. Circadian regulation of gene expression (i.e., the levels of specific proteins in cells) can be accomplished by clock control of transcription, mRNA stability, translation, and protein degradation. A particularly fascinating example of translational control by a circadian clock is that in the dinoflagellate alga, Gonyaulax (Rossini et al., 2003). However, we focus our discussion specifically on clock control of cyanobacterial gene expression at the level of transcription.In general, studies of circadian gene expression in eukaryotes have often used microarray analyses to show that a relatively small proportion of genes (~5%-15%) in eukaryotic genomes display rhythms in mRNA abundance. While microarray technology is well advanced, it should be noted that microarrays are not very sensitive to small changes of mRNA abundance, and moreover, they are not a good measure of rhythmic transcriptional activity for mRNAs that are either very unstable or very stable. Therefore, microarray results might not be reflective of transcriptional control in detail.

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“…A cikA null strain still exhibits circadian rhythmicity as monitored by bioluminescence produced from luciferase reporter genes; however, the circadian period is shortened by about 2 h, the amplitude of oscillation is greatly reduced, and, diagnostic of an input pathway defect, the ability to sense a 5 h pulse of darkness that resets the phase of circadian rhythms in the wild-type (WT) strain is almost completely abolished (Schmitz et al ., 2000). Other factors that affect environmental sensing by the clock have been identified (Kutsuna et al ., 1998;Ivleva et al ., 2005), but none has as great an effect as CikA on the ability to reset the clock other than a component of the circadian oscillator itself (Kiyohara et al ., 2005); the oscillator is presumably the target of the input pathway (Williams et al ., 2002).…”

Section: Introductionmentioning

confidence: 99%

“…The PsR domain of CikA cannot be phosphorylated by CikA HPK activity, consistent with absence from the PsR of the conserved aspartic acid present in bona fide RR proteins that receives a phosphoryl group from an HPK (Mutsuda et al ., 2003); thus, the PsR domain is not CikR. PsR domains may function like the receivers of RRs in regulating an adjacent domain, but use protein-protein interactions rather than phosphorylation to effect conformational change (O'Hara et al ., 1999;Williams et al ., 2002).…”

Section: Introductionmentioning

confidence: 99%

The pseudo‐receiver domain of CikA regulates the cyanobacterial circadian input pathway

Zhang

Dong

Golden

2006

Molecular Microbiology

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SummaryCikA (circadian input kinase) is a component of the cyanobacterial circadian clock that aids in synchronizing the endogenous oscillator with the external environment. cikA mutants of the prokaryotic circadian model organism Synechococcus elongatus PCC 7942 fail to reset the phase of the circadian rhythm of gene expression after an environmental time cue, and also exhibit reduced amplitude and shortened period of circadian oscillation. CikA has histidine protein kinase (HPK) activity that is modulated in vitro by GAF and pseudo -receiver (PsR) domains. Here we show that the PsR domain negatively regulates HPK activity in vivo and also serves as an interaction module to dock CikA at a specific subcellular location. Phenotypes conferred by alleles that encode CikA variants showed that all domains except the featureless Nterminus are required for CikA function. Overexpression of all alleles that encode the PsR domain, whether or not the HPK is functional, caused a dominant arrhythmic phenotype, whereas overexpressed variants that lack PsR did not. Subcellular localization of intact CikA identified a polar focus whereas a variant without PsR showed uniform distribution in the cell, consistent with a model in which PsR mediates interaction with other input pathway components.

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Structure and function from the circadian clock protein KaiA of Synechococcus elongatus : A potential clock input mechanism

Cited by 190 publications

References 38 publications

Roles of Two ATPase-Motif-containing Domains in Cyanobacterial Circadian Clock Protein KaiC

Roles of Two ATPase-Motif-containing Domains in Cyanobacterial Circadian Clock Protein KaiC

No Promoter Left Behind: Global Circadian Gene Expression in Cyanobacteria

The pseudo‐receiver domain of CikA regulates the cyanobacterial circadian input pathway

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