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概日リズムを司る時計タンパク質の相互作用の制御機構

柚木 康弘 Yunoki Yasuhiro 名古屋市立大学

2021.03.24

概要

生体内の概日リズムは生物時計によって制御されている。シアノバクテリアの概日リズムは 3 種類の時計タンパク質 (KaiA, KaiB, KaiC) のタンパク質間の相互作用によって制御されており、KaiCのリン酸化状態が 24 時間周期のリン酸化リズムを示す。

リン酸化リズム形成の中核を成す KaiC は 6 量体を形成しており、各サブユニットに 2 箇所のリン酸化サイトと 2 箇所のヌクレオチド結合サイトを有し、KaiC6 量体またはKai タンパク質複合体は溶液中では著しい多様性を有する可能性がある。こうした KaiC6 量体のミクロ状態と Kai タンパク質間の相互作用に関しては不明な点が多い。そこで本研究では、超分子質量分析を利用し、溶液の中の多数の分子の集団について、Kai タンパク質複合体を保ったまま、KaiC6 量体のリン酸化状態とヌクレオチド状態を明らかとするアプローチ法を開拓した。さらにこの方法を用いて KaiA-KaiC相互作用解析およびKaiB-KaiC 相互作用解析を行い、以下のことを明らかとした。

KaiC6 量体のとりうるヌクレオチドの状態は極めて限定されている。

KaiB とKaiC6 量体の相互作用には強い正の協同性が存在し、このことが、KaiC のリン酸化リズム形成、および概日リズムの発振制御に重要な役割を果たす。

KaiB との相互作用には、KaiC6 量体を構成する大半のサブユニットが高リン酸化状態である必要がある。

KaiC6 量体中の、脱リン酸化状態にあるサブユニットの KaiC の ATP 加水分解に伴って、C 末端領域が溶媒に露出し、KaiA との高い親和性を獲得する。

本研究の成果は、KaiC6 量体のリン酸化状態とヌクレオチド状態の連関、そしてサブユニット間の協同的な振る舞いが、Kai タンパク質間の相互作用の制御に重要であることを見出しており、分子集団として概日リズムを司る時計タンパク質の相互作用の制御機構の理解に資するものである。

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参考文献

1. J. S. O'Neill, A. B. Reddy, Circadian clocks in human red blood cells. Nature 469, 498- 503 (2011).

2. E. D. Weitzman, Circadian rhythms and episodic hormone secretion in man. Annu. Rev. Med. 27, 225-243 (1976).

3. M. M. Massin, K. Maeyns, N. Withofs, F. Ravet, P. Gérard, Circadian rhythm of heart rate and heart rate variability. Arch. Dis. Child. 83, 179-182 (2000).

4. F. C. Baker et al., Sleep and 24 hour body temperatures: a comparison in young men, naturally cycling women and women taking hormonal contraceptives. J. Physiol. 530, 565-574 (2001).

5. Y. Tahara, S. Shibata, Circadian rhythms of liver physiology and disease: experimental and clinical evidence. Nat. Rev. Gastroenterol. Hepatol. 13, 217-226 (2016).

6. C. S. Pittendrigh, Temporal organization: reflections of a Darwinian clock-watcher. Annu. Rev. Physiol. 55, 16-54 (1993).

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

8. J. S. van Zon, D. K. Lubensky, P. R. Altena, P. R. ten Wolde, An allosteric model of circadian KaiC phosphorylation. Proc Natl Acad Sci U S A 104, 7420-7425 (2007).

9. R. J. Konopka, S. Benzer, Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci U S A 68, 2112-2116 (1971).

10. M. W. Young, S. A. Kay, Time zones: a comparative genetics of circadian clocks. Nat Rev Genet 2, 702-715 (2001).

11. D. Bell-Pedersen et al., Circadian rhythms from multiple oscillators: lessons from diverse organisms. Nat Rev Genet 6, 544-556 (2005).

12. P. Lenz, L. Sogaard-Andersen, Temporal and spatial oscillations in bacteria. Nat. Rev. Microbiol. 9, 565-577 (2011).

13. M. Egli, C. H. Johnson, A circadian clock nanomachine that runs without transcription or translation. Curr. Opin. Neurobiol. 23, 732-740 (2013).

14. N. Kurabayashi, T. Hirota, Y. Harada, M. Sakai, Y. Fukada, Phosphorylation of mCRY2 at Ser557 in the hypothalamic suprachiasmatic nucleus of the mouse. Chronobiol. Int. 23, 129-134 (2006).

15. H. Yoshitane et al., Roles of CLOCK phosphorylation in suppression of E-box- dependent transcription. Mol. Cell. Biol. 29, 3675-3686 (2009).

16. N. Kon, Y. Sugiyama, H. Yoshitane, I. Kameshita, Y. Fukada, Cell-based inhibitor screening identifies multiple protein kinases important for circadian clock oscillations. Commun. Integr. Biol. 8, e982405 (2015).

17. N. Hayasaka et al., Salt-inducible kinase 3 regulates the mammalian circadian clock by destabilizing PER2 protein. Elife 6 (2017).

18. R. Pattanayek et al., Visualizing a circadian clock protein: crystal structure of KaiC and functional insights. Mol. Cell 15, 375-388 (2004).

19. M. Ishiura et al., Expression of a gene cluster kaiABC as a circadian feedback process in cyanobacteria. Science 281, 1519-1523 (1998).

20. M. Nakajima et al., Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro. Science 308, 414-415 (2005).

21. T. Nishiwaki et al., Role of KaiC phosphorylation in the circadian clock system of Synechococcus elongatus PCC 7942. Proc. Natl. Acad. Sci. USA 101, 13927-13932 (2004).

22. S. Ye, I. Vakonakis, T. R. Ioerger, A. C. LiWang, J. C. Sacchettini, Crystal structure of circadian clock protein KaiA from Synechococcus elongatus. J. Biol. Chem. 279, 20511-20518 (2004).

23. S. A. Villarreal et al., 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, 3311-3324 (2013).

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

25. R. Pattanayek et al., Analysis of KaiA-KaiC protein interactions in the cyano- bacterial circadian clock using hybrid structural methods. EMBO J. 25, 2017-2028 (2006).

26. J. Snijder et al., Structures of the cyanobacterial circadian oscillator frozen in a fully assembled state. Science 355, 1181-1184 (2017).

27. R. Tseng et al., Structural basis of the day-night transition in a bacterial circadian clock. Science 355, 1174-1180 (2017).

28. H. Iwasaki, T. Nishiwaki, Y. Kitayama, M. Nakajima, T. Kondo, KaiA-stimulated KaiC phosphorylation in circadian timing loops in cyanobacteria. Proc. Natl. Acad. Sci. USA 99, 15788-15793 (2002).

29. S. B. Williams, I. Vakonakis, S. S. Golden, A. C. LiWang, Structure and function from the circadian clock protein KaiA of Synechococcus elongatus: a potential clock input mechanism. Proc. Natl. Acad. Sci. USA 99, 15357-15362 (2002).

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

31. Y. Xu, T. Mori, C. H. Johnson, Cyanobacterial circadian clockwork: roles of KaiA, KaiB and the kaiBC promoter in regulating KaiC. EMBO J. 22, 2117-2126 (2003).

32. H. Kageyama et al., Cyanobacterial circadian pacemaker: Kai protein complex dynamics in the KaiC phosphorylation cycle in vitro. Mol. Cell 23, 161-171 (2006).

33. T. Mori et al., Elucidating the ticking of an in vitro circadian clockwork. PLoS Biol. 5, e93 (2007).

34. S. Akiyama, A. Nohara, K. Ito, Y. Maeda, Assembly and disassembly dynamics of the cyanobacterial periodosome. Mol. Cell 29, 703-716 (2008).

35. R. Pattanayek et al., Structures of KaiC circadian clock mutant proteins: a new phosphorylation site at T426 and mechanisms of kinase, ATPase and phosphatase. PLoS One 4, e7529 (2009).

36. R. Pattanayek, Y. Xu, A. Lamichhane, C. H. Johnson, M. Egli, An arginine tetrad as mediator of input-dependent and input-independent ATPases in the clock protein KaiC. Acta Crystallogr. D Biol. Crystallogr. 70, 1375-1390 (2014).

37. T. Nishiwaki, T. Kondo, Circadian autodephosphorylation of cyanobacterial clock protein KaiC occurs via formation of ATP as intermediate. J. Biol. Chem. 287, 18030- 18035 (2012).

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

39. M. Egli et al., Dephosphorylation of the core clock protein KaiC in the cyanobacterial KaiABC circadian oscillator proceeds via an ATP synthase mechanism. Biochemistry 51, 1547-1558 (2012).

40. J. Abe et al., Circadian rhythms. Atomic-scale origins of slowness in the cyanobacterial circadian clock. Science 349, 312-316 (2015).

41. R. Pattanayek et al., Combined SAXS/EM based models of the S. elongatus post- translational circadian oscillator and its interactions with the output His-kinase SasA. PLoS One 6, e23697 (2011).

42. M. Egli et al., Loop-loop interactions regulate KaiA-stimulated KaiC phosphorylation in the cyanobacterial KaiABC circadian clock. Biochemistry 52, 1208-1220 (2013).

43. T. Nishiwaki et al., A sequential program of dual phosphorylation of KaiC as a basis for circadian rhythm in cyanobacteria. EMBO J. 26, 4029-4037 (2007).

44. K. Oyama, C. Azai, K. Nakamura, S. Tanaka, K. Terauchi, Conversion between two conformational states of KaiC is induced by ATP hydrolysis as a trigger for cyanobacterial circadian oscillation. Sci. Rep. 6, 32443 (2016).

45. K. Oyama, C. Azai, J. Matsuyama, K. Terauchi, Phosphorylation at Thr432 induces structural destabilization of the CII ring in the circadian oscillator KaiC. FEBS Lett. 592, 36-45 (2018).

46. F. Hayashi et al., Stoichiometric interactions between cyanobacterial clock proteins KaiA and KaiC. Biochem. Biophys. Res. Commun. 316, 195-202 (2004).

47. F. Hayashi et al., Roles of two ATPase-motif-containing domains in cyanobacterial circadian clock protein KaiC. J. Biol. Chem. 279, 52331-52337 (2004).

48. R. Iwase et al., Functionally important substructures of circadian clock protein KaiB in a unique tetramer complex. J. Biol. Chem. 280, 43141-43149 (2005).

49. S. J. Valencia et al., Phase-dependent generation and transmission of time information by the KaiABC circadian clock oscillator through SasA-KaiC interaction in cyanobacteria. Genes Cells 17, 398-419 (2012).

50. T. Iida et al., Importance of the monomer-dimer-tetramer interconversion of the clock protein KaiB in the generation of circadian oscillations in cyanobacteria. Genes Cells 20, 173-190 (2015).

51. C. Phong, J. S. Markson, C. M. Wilhoite, M. J. Rust, Robust and tunable circadian rhythms from differentially sensitive catalytic domains. Proc. Natl. Acad. Sci. USA 110, 1124-1129 (2013).

52. J. Lin, J. Chew, U. Chockanathan, M. J. Rust, Mixtures of opposing phosphorylations within hexamers precisely time feedback in the cyanobacterial circadian clock. Proc. Natl. Acad. Sci. USA 111, E3937-3945 (2014).

53. Y. G. Chang et al., Circadian rhythms. A protein fold switch joins the circadian oscillator to clock output in cyanobacteria. Science 349, 324-328 (2015).

54. Y. G. Chang, N. W. Kuo, R. Tseng, A. LiWang, 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, 14431-14436 (2011).

55. R. Pattanayek, K. K. Yadagiri, M. D. Ohi, M. Egli, Nature of KaiB-KaiC binding in the cyanobacterial circadian oscillator. Cell Cycle 12, 810-817 (2013).

56. A. Gutu, E. K. O'Shea, Two antagonistic clock-regulated histidine kinases time the activation of circadian gene expression. Mol. Cell 50, 288-294 (2013).

57. T. Osanai et al., Alteration of cyanobacterial sugar and amino acid metabolism by overexpression hik8, encoding a KaiC-associated histidine kinase. Environ. Microbiol. 17, 2430-2440 (2015).

58. R. K. Shultzaberger, J. S. Boyd, S. Diamond, R. J. Greenspan, S. S. Golden, Giving Time Purpose: The Synechococcus elongatus Clock in a Broader Network Context. Annu. Rev. Genet. 49, 485-505 (2015).

59. R. Murakami et al., The roles of the dimeric and tetrameric structures of the clock protein KaiB in the generation of circadian oscillations in cyanobacteria. J. Biol. Chem. 287, 29506-29515 (2012).

60. R. Murakami et al., Atomic force microscopy analysis of SasA-KaiC complex formation involved in information transfer from the KaiABC clock machinery to the output pathway in cyanobacteria. Genes Cells 10.1111/gtc.12574 (2018).

61. A. Mukaiyama et al., Conformational rearrangements of the C1 ring in KaiC measure the timing of assembly with KaiB. Sci. Rep. 8, 8803 (2018).

62. S. I. Koda, S. Saito, An alternative interpretation of the slow KaiB-KaiC binding of the cyanobacterial clock proteins. Sci. Rep. 10, 10439 (2020).

63. R. Pattanayek, M. Egli, Protein-Protein Interactions in the Cyanobacterial Circadian Clock: Structure of KaiA Dimer in Complex with C-Terminal KaiC Peptides at 2.8 A Resolution. Biochemistry 54, 4575-4578 (2015).

64. I. Vakonakis, A. C. LiWang, 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. USA 101, 10925-10930 (2004).

65. I. Vakonakis, D. A. Klewer, S. B. Williams, S. S. Golden, A. C. LiWang, Structure of the N-terminal domain of the circadian clock-associated histidine kinase SasA. J. Mol. Biol. 342, 9-17 (2004).

66. T. Uzumaki et al., Crystal structure of the C-terminal clock-oscillator domain of the cyanobacterial KaiA protein. Nat. Struct. Mol. Biol. 11, 623-631 (2004).

67. Q. Chen, S. Liu, L. Yang, L. Zhang, J. Li, The reversible function switching of the circadian clock protein KaiA is encoded in its structure. Biochim Biophys Acta Gen Subj 1861, 2535-2542 (2017).

68. J. Li, Y. Huang, Z. Su, S. Liu, The recovery of KaiA's activity depends on its N- terminal domain and KaiB in the cyanobacterial circadian clock. Biochem. Biophys. Res. Commun. 524, 123-128 (2020).

69. M. Sugiyama et al., Structural characterization of the circadian clock protein complex composed of KaiB and KaiC by inverse contrast-matching small-angle neutron scattering. Sci. Rep. 6, 35567 (2016).

70. M. Yagi-Utsumi et al., Supramolecular tholos-like architecture constituted by archaeal proteins without functional annotation. Sci. Rep. 10, 1540 (2020).

71. M. Sugiyama et al., SAXS and SANS observations of abnormal aggregation of human alpha-crystallin. Chem. Biodivers. 7, 1380-1388 (2010).

72. M. Sugiyama et al., Solution structure of variant H2A.Z.1 nucleosome investigated by small-angle X-ray and neutron scatterings. Biochem Biophys Rep 4, 28-32 (2015).

73. N. Shimizu et al. (2016) Software development for analysis of small-angle x-ray scattering data. in AIP Conference Proceedings (AIP Publishing LLC), p 050017.

74. D. Orthaber, A. Bergmann, O. Glatter, SAXS experiments on absolute scale with Kratky systems using water as a secondary standard. Journal of Applied Crystallography 33, 218-225 (2000).

75. C. Dewhurst, GRASP (Institut Laue-Langevin); https://www.ill.eu/users/support- labs-infrastructure/software-scientific-tools/grasp. (2020).

76. J. A. Maier et al., ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J. Chem. Theory Comput. 11, 3696-3713 (2015).

77. W. L. Jorgensen, J. Chandrasekhar, J. D. Madura, R. W. Impey, M. L. Klein, Comparison of simple potential functions for simulating liquid water. The Journal of chemical physics 79, 926-935 (1983).

78. H. J. Berendsen, D. van der Spoel, R. van Drunen, GROMACS: a message-passing parallel molecular dynamics implementation. Computer physics communications 91, 43-56 (1995).

79. E. Lindahl, B. Hess, D. Van Der Spoel, GROMACS 3.0: a package for molecular simulation and trajectory analysis. Molecular modeling annual 7, 306-317 (2001).

80. D. Van Der Spoel et al., GROMACS: fast, flexible, and free. J. Comput. Chem. 26, 1701-1718 (2005).

81. B. Hess, C. Kutzner, D. Van Der Spoel, E. Lindahl, GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435-447 (2008).

82. S. Pronk et al., GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29, 845-854 (2013).

83. S. Páll, M. J. Abraham, C. Kutzner, B. Hess, E. Lindahl (2014) Tackling exascale software challenges in molecular dynamics simulations with GROMACS. in International conference on exascale applications and software (Springer), pp 3-27.

84. M. J. Abraham et al., GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1, 19-25 (2015).

85. P. H. Hünenberger, A. E. Mark, W. F. van Gunsteren, Fluctuation and cross- correlation analysis of protein motions observed in nanosecond molecular dynamics simulations. J. Mol. Biol. 252, 492-503 (1995).

86. I. Vakonakis et al., NMR structure of the KaiC-interacting C-terminal domain of KaiA, a circadian clock protein: implications for KaiA-KaiC interaction. Proc Natl Acad Sci U S A 101, 1479-1484 (2004).

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