Skip to main content

Mechanistic Aspects of the Cyanobacterial Circadian Clock

  • 582 Accesses

Abstract

Circadian clocks are intracellular systems that provide an internal representation of time to regulate metabolism in preparation for day and night. A variety of mechanisms arose throughout the evolutionary tree as an adaptation to predictable daily swings in ambient light and temperature. In this chapter we will focus exclusively on the circadian clock shared by the cyanobacteria Synechococcus elongatus and Thermosynechococcus elongatus, with a noncomprehensive scope that emphasizes mechanism. As will hopefully become apparent here, the cyanobacterial system is valuable to the broader circadian clocks field because it yields conceptual insights into biological timekeeping at a level of detail higher and more comprehensive than those achieved so far in other systems. Major takeaways of this chapter include the following: (1) coordination of moving clock components is achieved through long-range allostery mediated by changes in structure and dynamics such that the clock runs clockwise and not counterclockwise, and (2) the fold-switching behavior of a clock protein underpins circadian rhythms of gene expression.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-030-72158-9_4
  • Chapter length: 11 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   169.00
Price excludes VAT (USA)
  • ISBN: 978-3-030-72158-9
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   219.99
Price excludes VAT (USA)
Hardcover Book
USD   219.99
Price excludes VAT (USA)
Fig. 1

Bibliography

  • Abe J, Hiyama TB, Mukaiyama A et al (2015) Circadian rhythms. Atomic-scale origins of slowness in the cyanobacterial circadian clock. Science 349(6245):312–316

    CAS  PubMed  CrossRef  Google Scholar 

  • Chang Y-G, Kuo N-W, Tseng R, LiWang A (2011) Flexibility of the C-terminal, or CII, ring of KaiC governs the rhythm of the circadian clock of cyanobacteria. Proc Natl Acad Sci U S A 108(35):14431–14436

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Chang Y-G, Tseng R, Kuo N-W, LiWang A (2012) Rhythmic ring-ring stacking drives the circadian oscillator clockwise. Proc Natl Acad Sci U S A 109(42):16847–16851

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Chang Y-G, Cohen SE, Phong C et al (2015) Circadian rhythms. A protein fold switch joins the circadian oscillator to clock output in cyanobacteria. Science 349(6245):324–328

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Chavan AG, Ernst DC, Fang M et al (2020) Reconstitution of an intact clock that generates circadian DNA binding in vitro. BioRxiv

    Google Scholar 

  • Chow GK, Chavan AG, Heisler JC, Chang Y-G, LiWang A, Britt RD (2020) Monitoring protein-protein interactions in the cyanobacterial circadian clock in real time via electron paramagnetic resonance spectroscopy. Biochemistry 59(26):2387–2400

    CAS  PubMed  CrossRef  Google Scholar 

  • Garces RG, Wu N, Gillon W, Pai EF (2004) Anabaena circadian clock proteins KaiA and KaiB reveal a potential common binding site to their partner KaiC. EMBO J 23(8):1688–1698

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Gutu A, O’Shea EK (2013) Two antagonistic clock-regulated histidine kinases time the activation of circadian gene expression. Mol Cell 50(2):288–294

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Hayashi F, Itoh N, Uzumaki T et al (2004) Roles of two ATPase-motif-containing domains in cyanobacterial circadian clock protein KaiC. J Biol Chem 279(50):52331–52337

    CAS  PubMed  CrossRef  Google Scholar 

  • Heisler J, Chavan A, Chang Y-G, LiWang A (2019) Real-time in vitro fluorescence anisotropy of the cyanobacterial circadian clock. Method Protoc 2(2):42

    CAS  CrossRef  Google Scholar 

  • Heisler J, Swan JA, Palacios JG et al (2020) Structural mimicry confers robustness in the cyanobacterial circadian clock. BioRxiv

    Google Scholar 

  • Hitomi K, Oyama T, Han S, Arvai AS, Getzoff ED (2005) Tetrameric architecture of the circadian clock protein KaiB. A novel interface for intermolecular interactions and its impact on the circadian rhythm. J Biol Chem 280(19):19127–19135

    CAS  PubMed  CrossRef  Google Scholar 

  • Hong L, Vani BP, Thiede EH, Rust MJ, Dinner AR (2018) Molecular dynamics simulations of nucleotide release from the circadian clock protein KaiC reveal atomic-resolution functional insights. Proc Natl Acad Sci U S A 115(49):E11475–E11484

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Hong L, Lavrentovich DO, Chavan A et al (2020) Bayesian modeling reveals metabolite-dependent ultrasensitivity in the cyanobacterial circadian clock. Mol Syst Biol 16(6):e9355

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Ishiura M, Kutsuna S, Aoki S et al (1998) Expression of a gene cluster kaiABC as a circadian feedback process in cyanobacteria. Science 281(5382):1519–1523

    CAS  PubMed  CrossRef  Google Scholar 

  • Ito-Miwa K, Furuike Y, Akiyama S, Kondo T (2020) Tuning the circadian period of cyanobacteria up to 6.6 days by the single amino acid substitutions in KaiC. Proc Natl Acad Sci U S A 117(34):20926–20931

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Iwasaki H, Taniguchi Y, Ishiura M, Kondo T (1999) Physical interactions among circadian clock proteins KaiA, KaiB and KaiC in cyanobacteria. EMBO J 18(5):1137–1145

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Iwasaki H, Williams SB, Kitayama Y, Ishiura M, Golden SS, Kondo T (2000) A kaiC-interacting sensory histidine kinase, SasA, necessary to sustain robust circadian oscillation in cyanobacteria. Cell 101(2):223–233

    CAS  PubMed  CrossRef  Google Scholar 

  • Iwasaki H, Nishiwaki T, Kitayama Y, Nakajima M, Kondo T (2002) KaiA-stimulated KaiC phosphorylation in circadian timing loops in cyanobacteria. Proc Natl Acad Sci U S A 99(24):15788–15793

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Iwase R, Imada K, Hayashi F et al (2005) Functionally important substructures of circadian clock protein KaiB in a unique tetramer complex. J Biol Chem 280(52):43141–43149

    CAS  PubMed  CrossRef  Google Scholar 

  • Kageyama H, Kondo T, Iwasaki H (2003) Circadian formation of clock protein complexes by KaiA, KaiB, KaiC, and SasA in cyanobacteria. J Biol Chem 278(4):2388–2395

    CAS  PubMed  CrossRef  Google Scholar 

  • Kaur M, Ng A, Kim P, Diekman C, Kim Y-I (2019) Cika modulates the effect of kaia on the period of the circadian oscillation in kaic phosphorylation. J Biol Rhythm 34(2):218–223

    CAS  CrossRef  Google Scholar 

  • Kim Y-I, Dong G, Carruthers CW, Golden SS, LiWang A (2008) The day/night switch in KaiC, a central oscillator component of the circadian clock of cyanobacteria. Proc Natl Acad Sci U S A 105(35):12825–12830

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Kim Y-I, Vinyard DJ, Ananyev GM, Dismukes GC, Golden SS (2012) Oxidized quinones signal onset of darkness directly to the cyanobacterial circadian oscillator. Proc Natl Acad Sci U S A 109(44):17765–17769

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Kim P, Porr B, Mori T et al (2020) Cika, an input pathway component, senses the oxidized quinone signal to generate phase delays in the cyanobacterial circadian clock. J Biol Rhythm 35(3):227–234

    CAS  CrossRef  Google Scholar 

  • Kitayama Y, Iwasaki H, Nishiwaki T, Kondo T (2003) KaiB functions as an attenuator of KaiC phosphorylation in the cyanobacterial circadian clock system. EMBO J 22(9):2127–2134

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Kondo T, Strayer CA, Kulkarni RD et al (1993) Circadian rhythms in prokaryotes: luciferase as a reporter of circadian gene expression in cyanobacteria. Proc Natl Acad Sci U S A 90(12):5672–5676

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Leipe DD, Aravind L, Grishin NV, Koonin EV (2000) The bacterial replicative helicase DnaB evolved from a RecA duplication. Genome Res 10(1):5–16

    CAS  PubMed  Google Scholar 

  • Leypunskiy E, Lin J, Yoo H, Lee U, Dinner AR, Rust MJ (2017) The cyanobacterial circadian clock follows midday in vivo and in vitro. eLife 6:e23539

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • Lin J, Chew J, Chockanathan U, Rust MJ (2014) Mixtures of opposing phosphorylations within hexamers precisely time feedback in the cyanobacterial circadian clock. Proc Natl Acad Sci U S A 111(37):E3937–E3945

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Ma L, Ranganathan R (2012) Quantifying the rhythm of KaiB-C interaction for in vitro cyanobacterial circadian clock. PLoS One 7(8):e42581

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Mori T, Sugiyama S, Byrne M, Johnson CH, Uchihashi T, Ando T (2018) Revealing circadian mechanisms of integration and resilience by visualizing clock proteins working in real time. Nat Commun 9(1):3245

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Murakami R, Miyake A, Iwase R, Hayashi F, Uzumaki T, Ishiura M (2008) ATPase activity and its temperature compensation of the cyanobacterial clock protein KaiC. Genes Cells 13(4):387–395

    CAS  PubMed  CrossRef  Google Scholar 

  • Murzin AG (2008) Biochemistry. Metamorphic proteins. Science 320(5884):1725–1726

    CAS  PubMed  CrossRef  Google Scholar 

  • Mutoh R, Nishimura A, Yasui S, Onai K, Ishiura M (2013) The ATP-mediated regulation of KaiB-KaiC interaction in the cyanobacterial circadian clock. PLoS One 8(11):e80200

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Nakajima M, Imai K, Ito H et al (2005) Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro. Science 308(5720):414–415

    CAS  PubMed  CrossRef  Google Scholar 

  • Nishiwaki T, Iwasaki H, Ishiura M, Kondo T (2000) Nucleotide binding and autophosphorylation of the clock protein KaiC as a circadian timing process of cyanobacteria. Proc Natl Acad Sci U S A 97(1):495–499

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Nishiwaki T, Satomi Y, Nakajima M et al (2004) Role of KaiC phosphorylation in the circadian clock system of Synechococcus elongatus PCC 7942. Proc Natl Acad Sci U S A 101(38):13927–13932

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Nishiwaki T, Satomi Y, Kitayama Y et al (2007) A sequential program of dual phosphorylation of KaiC as a basis for circadian rhythm in cyanobacteria. EMBO J 26(17):4029–4037

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Nishiwaki-Ohkawa T, Kitayama Y, Ochiai E, Kondo T (2014) Exchange of ADP with ATP in the CII ATPase domain promotes autophosphorylation of cyanobacterial clock protein KaiC. Proc Natl Acad Sci U S A 111(12):4455–4460

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Pattanayek R, Egli M (2015) Protein-protein interactions in the cyanobacterial circadian clock: structure of KaiA dimer in complex with C-terminal KaiC peptides at 2.8 Å resolution. Biochemistry 54(30):4575–4578

    CAS  PubMed  CrossRef  Google Scholar 

  • Pattanayek R, Wang J, Mori T, Xu Y, Johnson CH, Egli M (2004) Visualizing a circadian clock protein: crystal structure of KaiC and functional insights. Mol Cell 15(3):375–388

    CAS  PubMed  CrossRef  Google Scholar 

  • Pattanayek R, Williams DR, Pattanayek S et al (2008) Structural model of the circadian clock KaiB-KaiC complex and mechanism for modulation of KaiC phosphorylation. EMBO J 27(12):1767–1778

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Pattanayek R, Yadagiri KK, Ohi MD, Egli M (2013) Nature of KaiB-KaiC binding in the cyanobacterial circadian oscillator. Cell Cycle 12(5):810–817

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Phong C, Markson JS, Wilhoite CM, Rust MJ (2013) Robust and tunable circadian rhythms from differentially sensitive catalytic domains. Proc Natl Acad Sci U S A 110(3):1124–1129

    CAS  PubMed  CrossRef  Google Scholar 

  • Rust MJ, Markson JS, Lane WS, Fisher DS, O’Shea EK (2007) Ordered phosphorylation governs oscillation of a three-protein circadian clock. Science 318(5851):809–812

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Rust MJ, Golden SS, O’Shea EK (2011) Light-driven changes in energy metabolism directly entrain the cyanobacterial circadian oscillator. Science 331(6014):220–223

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Smith RM, Williams SB (2006) Circadian rhythms in gene transcription imparted by chromosome compaction in the cyanobacterium Synechococcus elongatus. Proc Natl Acad Sci U S A 103(22):8564–8569

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Snijder J, Burnley RJ, Wiegard A et al (2014) Insight into cyanobacterial circadian timing from structural details of the KaiB-KaiC interaction. Proc Natl Acad Sci U S A 111(4):1379–1384

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Snijder J, Schuller JM, Wiegard A et al (2017) Structures of the cyanobacterial circadian oscillator frozen in a fully assembled state. Science 355(6330):1181–1184

    CAS  PubMed  CrossRef  Google Scholar 

  • Taniguchi Y, Yamaguchi A, Hijikata A et al (2001) Two KaiA-binding domains of cyanobacterial circadian clock protein KaiC. FEBS Lett 496(2–3):86–90

    CAS  PubMed  CrossRef  Google Scholar 

  • Tomita J, Nakajima M, Kondo T, Iwasaki H (2005) No transcription-translation feedback in circadian rhythm of KaiC phosphorylation. Science 307(5707):251–254

    CAS  PubMed  CrossRef  Google Scholar 

  • Tseng R, Chang Y-G, Bravo I et al (2014) Cooperative KaiA-KaiB-KaiC interactions affect KaiB/SasA competition in the circadian clock of cyanobacteria. J Mol Biol 426(2):389–402

    CAS  PubMed  CrossRef  Google Scholar 

  • Tseng R, Goularte NF, Chavan A et al (2017) Structural basis of the day-night transition in a bacterial circadian clock. Science 355(6330):1174–1180

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Vakonakis I, LiWang AC (2004) Structure of the C-terminal domain of the clock protein KaiA in complex with a KaiC-derived peptide: implications for KaiC regulation. Proc Natl Acad Sci U S A 101(30):10925–10930

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Vakonakis I, Klewer DA, Williams SB, Golden SS, LiWang AC (2004) Structure of the N-terminal domain of the circadian clock-associated histidine kinase SasA. J Mol Biol 342(1):9–17

    CAS  PubMed  CrossRef  Google Scholar 

  • van Zon JS, Lubensky DK, Altena PRH, ten Wolde PR (2007) An allosteric model of circadian KaiC phosphorylation. Proc Natl Acad Sci U S A 104(18):7420–7425

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • Villarreal SA, Pattanayek R, Williams DR et al (2013) CryoEM and molecular dynamics of the circadian KaiB-KaiC complex indicates that KaiB monomers interact with KaiC and block ATP binding clefts. J Mol Biol 425(18):3311–3324

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Williams SB, Vakonakis I, Golden SS, LiWang AC (2002) Structure and function from the circadian clock protein KaiA of Synechococcus elongatus: a potential clock input mechanism. Proc Natl Acad Sci U S A 99(24):15357–15362

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Xu Y, Piston DW, Johnson CH (1999) A bioluminescence resonance energy transfer (BRET) system: application to interacting circadian clock proteins. Proc Natl Acad Sci U S A 96(1):151–156

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Xu Y, Mori T, Johnson CH (2003) Cyanobacterial circadian clockwork: roles of KaiA, KaiB and the kaiBC promoter in regulating KaiC. EMBO J 22(9):2117–2126

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Xu Y, Mori T, Pattanayek R, Pattanayek S, Egli M, Johnson CH (2004) Identification of key phosphorylation sites in the circadian clock protein KaiC by crystallographic and mutagenetic analyses. Proc Natl Acad Sci U S A 101(38):13933–13938

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Ye S, Vakonakis I, Ioerger TR, LiWang AC, Sacchettini JC (2004) Crystal structure of circadian clock protein KaiA from Synechococcus elongatus. J Biol Chem 279(19):20511–20518

    CAS  PubMed  CrossRef  Google Scholar 

  • Yoshida T, Murayama Y, Ito H, Kageyama H, Kondo T (2009) Nonparametric entrainment of the in vitro circadian phosphorylation rhythm of cyanobacterial KaiC by temperature cycle. Proc Natl Acad Sci U S A 106(5):1648–1653

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

Download references

Acknowledgments

This work was supported by US National Institutes of Health grants R35GM118290 (to S.S.G.) and R01GM107521 (to A.L.), the Department of the Army Research Office grant W911NF-17-1-0434 (to A.L.), and NSF-CREST: Center for Cellular and Biomolecular Machines at the University of California, Merced (NSF-HRD-1547848).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andy LiWang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Verify currency and authenticity via CrossMark

Cite this chapter

Golden, S.S., LiWang, A. (2021). Mechanistic Aspects of the Cyanobacterial Circadian Clock. In: Johnson, C.H., Rust, M.J. (eds) Circadian Rhythms in Bacteria and Microbiomes. Springer, Cham. https://doi.org/10.1007/978-3-030-72158-9_4

Download citation