title: KaiC intersubunit communication facilitates robustness of circadian rhythms in cyanobacteria.
abstract: The cyanobacterial circadian clock is the only model clock to have been reconstituted in vitro. KaiC, the central clock component, is a homohexameric ATPase with autokinase and autophosphatase activities. Changes in phosphorylation state have been proposed to switch KaiC's activity between autokinase and autophosphatase. Here we analyse the molecular mechanism underlying the regulation of KaiC's activity, in the context of its hexameric structure. We reconstitute KaiC hexamers containing different variant protomers, and measure their autophosphatase and autokinase activities. We identify two types of regulatory mechanisms with distinct functions. First, local interactions between adjacent phosphorylation sites regulate KaiC's activities, coupling the ATPase and nucleotide-binding states at subunit interfaces of the CII domain. Second, the phosphorylation states of the protomers affect the overall activity of KaiC hexamers via intersubunit communication. Our findings indicate that intra-hexameric interactions play an important role in sustaining robust circadian rhythmicity.
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University and CREST, Japan Science and Technology Agency (JST), Furo-cho, Chikusa-ku, Nagoya 464 8602, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Kitayama
authors.forename: Taeko
authors.initials: T
authors.lastname: Nishiwaki-Ohkawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sugisawa
authors.forename: Takao
authors.initials: T
authors.lastname: Kondo
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002940:Circadian Rhythm / Q000502:physiology*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D046940:Synechococcus / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; C114271:KaiC protein, cyanobacteria; D009711:Nucleotides; D021122:Protein Subunits; D011994:Recombinant Proteins