Structures of the cyanobacterial circadian oscillator frozen in a fully assembled state

Snijder, Joost; Schuller, Jan M.; Wiegard, Anika; Lössl, Philip; Schmelling, Nicolas; Axmann, Ilka M.; Plitzko, Jürgen M.; Förster, Friedrich; Heck, Albert J. R.

doi:10.1126/science.aag3218

Cited by 114 publications

(152 citation statements)

References 51 publications

(47 reference statements)

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…Altogether, KaiC hexamers phosphorylate and dephosphorylate rhythmically during the course of a day. 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]. The binding of oxidized quinones to KaiA has been suggested to stop the clock directly by causing KaiA aggregation [34, 35].…”

Section: Introductionmentioning

confidence: 99%

Minimal tool set for a prokaryotic circadian clock

Schmelling

Lehmann

Chaudhury³

et al. 2017

BMC Evol Biol

Self Cite

View full text Add to dashboard Cite

BackgroundCircadian clocks are found in organisms of almost all domains including photosynthetic Cyanobacteria, whereby large diversity exists within the protein components involved. In the model cyanobacterium Synechococcus elongatus PCC 7942 circadian rhythms are driven by a unique KaiABC protein clock, which is embedded in a network of input and output factors. Homologous proteins to the KaiABC clock have been observed in Bacteria and Archaea, where evidence for circadian behavior in these domains is accumulating. However, interaction and function of non-cyanobacterial Kai-proteins as well as homologous input and output components remain mainly unclear.ResultsUsing a universal BLAST analyses, we identified putative KaiC-based timing systems in organisms outside as well as variations within Cyanobacteria. A systematic analyses of publicly available microarray data elucidated interesting variations in circadian gene expression between different cyanobacterial strains, which might be correlated to the diversity of genome encoded clock components. Based on statistical analyses of co-occurrences of the clock components homologous to Synechococcus elongatus PCC 7942, we propose putative networks of reduced and fully functional clock systems. Further, we studied KaiC sequence conservation to determine functionally important regions of diverged KaiC homologs. Biochemical characterization of exemplary cyanobacterial KaiC proteins as well as homologs from two thermophilic Archaea demonstrated that kinase activity is always present. However, a KaiA-mediated phosphorylation is only detectable in KaiC1 orthologs.ConclusionOur analysis of 11,264 genomes clearly demonstrates that components of the Synechococcus elongatus PCC 7942 circadian clock are present in Bacteria and Archaea. However, all components are less abundant in other organisms than Cyanobacteria and KaiA, Pex, LdpA, and CdpA are only present in the latter. Thus, only reduced KaiBC-based or even simpler, solely KaiC-based timing systems might exist outside of the cyanobacterial phylum, which might be capable of driving diurnal oscillations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-017-0999-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Minimal tool set for a prokaryotic circadian clock

Schmelling

Lehmann

Chaudhury³

et al. 2017

BMC Evol Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…We assume that KaiB can bind to only C1 in the BC state and that KaiA can bind strongly to the KaiB-C1 complex, which eventually results in the sequestration of KaiA from C2. Moreover, the conformational transition from BI to BC state is assumed to be promoted when C1 binds abundant ADP rather than ATP, as suggested experimentally [20,21,32,33]. Under this assumption, switching between phosphorylation and dephosphorylation is controlled by the ADP/ATP exchange in C1 because the exchange determines the amount of ADP in C1, which is the trigger of the conformational transition from BI to BC state.…”

Section: Model Setupmentioning

confidence: 99%

“…During the oscillation, C1 and C2 allosterically communicate and regulate the (dis)assembly of KaiA and KaiB through several domain-specific conformational transitions. For example, recent studies on the KaiABC complex [20,21] have revealed that KaiB can bind to an ADP-bound conformation of C1 [22]. On the other hand, C2 has the buried and exposed states of the C-terminal tail [14,15], and KaiA can bind only in the latter state.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sufficiency of unidirectional allostery in KaiC in generating the cyanobacterial circadian rhythm

Koda

Saito

2020

Preprint

View full text Add to dashboard Cite

The clock protein of cyanobacteria KaiC forms a homohexamer with two ring-shaped domains, C1 and C2. These domains undergo several domain-specific conformational transitions and allosterically communicate to generate a circadian rhythm. Interestingly, experiments show a possibility that C2 is independent of C1. However, detailed interplay among them remains elusive. Here we propose a mathematical model, which explicitly considers the interplay. The allostery in KaiC is here modeled to be unidirectional from C2 to C1. We demonstrate that the unidirectional allostery is sufficient for the circadian rhythm by showing the quantitative reproducibility of various experimental data, including temperature dependence of both phosphorylation oscillation and ATPase activity. Based on the present model, we further discuss possible functional roles of the unidirectional allostery particularly in the period robustness against both protein concentration and temperature. * koda@ims.ac.jp † shinji@ims.ac.jp Circadian clocks are biological timing systems embedded in most living organisms and enable the organisms to anticipate daily changes in the environment and to adjust their biological activities. The simplest circadian clock is that of cyanobacteria, where the core oscillator is composed of only three proteins, KaiA, KaiB, and KaiC[1]. Interestingly, this circadian rhythm can be reconstituted in a test tube just by mixing the three proteins with ATP, which results in a nearly 24-hour periodic oscillation of phosphorylation of KaiC[2]. In addition to this self-sustaining oscillation, the KaiABC oscillator possesses several fundamental functions as a biological clock. For example, the period of the oscillator is robust against environmental perturbations such as temperature[2] and concentrations of the proteins[3]. The oscillator is further entrained by various periodic environmental changes, including temperature[4] and ATP/ADP ratio in buffer[5]. This simple yet functional system has thus attracted considerable interests in elucidating the molecular origins of circadian rhythm. KaiC is the central component in the KaiABC oscillator, and in the presence of ATP, forms a homohexamer with two ring-shaped domains, C1 and C2[6, 7]. Both C1 and C2 have ATPase activities. C2 also has autokinase and autophosphatase activities, where two residues near the ATP binding site in C2, Ser431 and Thr432, are phosphorylated and dephosphorylated. With the help of KaiA and KaiB, (de)phosphorylation occurs in the following order: ST → SpT → pSpT → pST → ST[8, 9], where S/pS and T/pT are the unphosphorylated/phosphorylated states of Ser431 and Thr432, respectively. KaiA promotes phosphorylation of KaiC[10, 11] by acting on the C-terminal tail of C2[12-15]. It facilitates the exchange of bound ADP with exogenous ATP[16], suggesting that the enhanced ADP/ATP exchange supplies abundant phosphate for phosphorylation reactions in the form of ATP, and shifts the equilibrium of phosphorylation reactions toward phosphorylated states.KaiB, on the other hand...

show abstract

“…KaiB, on the other hand, inhibits KaiA activity 13,14 , which results in the dephosphorylation of C2. Specifically, after adequate phosphorylation of C2, KaiB binds to C1 and strongly sequesters KaiA from C2 by forming the C1-KaiB-KaiA complex 15 , which has recently been observed directly 16,17 .…”

Section: Introductionmentioning

confidence: 98%

An alternative interpretation of the slow KaiB-KaiC binding of the cyanobacterial clock proteins

Koda

Saito

2020

Preprint

View full text Add to dashboard Cite

The biological clock of cyanobacteria is composed of three proteins, KaiA, KaiB, and KaiC. The KaiB-KaiC binding brings the slowness into the system, which is essential for the long period of the circadian rhythm.However, there is no consensus as to the origin of the slowness due to the pre-binding conformational transition of either KaiB or KaiC. In this study, we propose a simple KaiB-KaiC binding scheme in a hexameric form with an attractive interaction between adjacent bound KaiB monomers, which is independent of KaiB's conformational change. We then show that the present scheme can explain several important experimental results on the binding, including that used as evidence for the slow conformational transition of KaiB. The present result thus indicates that the slowness arises from KaiC rather than KaiB.

show abstract

Structures of the cyanobacterial circadian oscillator frozen in a fully assembled state

Cited by 114 publications

References 51 publications

Minimal tool set for a prokaryotic circadian clock

Minimal tool set for a prokaryotic circadian clock

Sufficiency of unidirectional allostery in KaiC in generating the cyanobacterial circadian rhythm

An alternative interpretation of the slow KaiB-KaiC binding of the cyanobacterial clock proteins

Contact Info

Product

Resources

About