title: Circadian rhythms. Atomic-scale origins of slowness in the cyanobacterial circadian clock.
abstract: Circadian clocks generate slow and ordered cellular dynamics but consist of fast-moving bio-macromolecules; consequently, the origins of the overall slowness remain unclear. We identified the adenosine triphosphate (ATP) catalytic region [adenosine triphosphatase (ATPase)] in the amino-terminal half of the clock protein KaiC as the minimal pacemaker that controls the in vivo frequency of the cyanobacterial clock. Crystal structures of the ATPase revealed that the slowness of this ATPase arises from sequestration of a lytic water molecule in an unfavorable position and coupling of ATP hydrolysis to a peptide isomerization with high activation energy. The slow ATPase is coupled with another ATPase catalyzing autodephosphorylation in the carboxyl-terminal half of KaiC, yielding the circadian response frequency of intermolecular interactions with other clock-related proteins that influences the transcription and translation cycle.
authors.affiliation: Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Abe
authors.affiliation: Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan.
authors.forename: Takuya B
authors.initials: TB
authors.lastname: Hiyama
authors.affiliation: Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Functional Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mukaiyama
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Seyoung
authors.initials: S
authors.lastname: Son
authors.affiliation: Department of Functional Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Theoretical and Computational Molecular Science, Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Mori
authors.affiliation: Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Functional Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Theoretical and Computational Molecular Science, Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Saito
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Osako
authors.affiliation: Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. PSL Research University, Chimie ParisTech, 75005 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Wolanin
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Yamashita
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Functional Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. akiyamas@ims.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Akiyama
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics; D000255:Adenosine Triphosphate / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D002384:Catalysis; D020134:Catalytic Domain; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D006868:Hydrolysis; D046940:Synechococcus / Q000201:enzymology / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; C114271:KaiC protein, cyanobacteria; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases