title: Intermolecular associations determine the dynamics of the circadian KaiABC oscillator.
abstract: Three proteins from cyanobacteria (KaiA, KaiB, and KaiC) can reconstitute circadian oscillations in vitro. At least three molecular properties oscillate during this reaction, namely rhythmic phosphorylation of KaiC, ATP hydrolytic activity of KaiC, and assembly/disassembly of intermolecular complexes among KaiA, KaiB, and KaiC. We found that the intermolecular associations determine key dynamic properties of this in vitro oscillator. For example, mutations within KaiB that alter the rates of binding of KaiB to KaiC also predictably modulate the period of the oscillator. Moreover, we show that KaiA can bind stably to complexes of KaiB and hyperphosphorylated KaiC. Modeling simulations indicate that the function of this binding of KaiA to the KaiB*KaiC complex is to inactivate KaiA's activity, thereby promoting the dephosphorylation phase of the reaction. Therefore, we report here dynamics of interaction of KaiA and KaiB with KaiC that determine the period and amplitude of this in vitro oscillator.
authors.affiliation: Departments of Biological Sciences and Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Ximing
authors.initials: X
authors.lastname: Qin
authors.forename: Mark
authors.initials: M
authors.lastname: Byrne
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.forename: Ping
authors.initials: P
authors.lastname: Zou
authors.forename: Dewight R
authors.initials: DR
authors.lastname: Williams
authors.forename: Hassane
authors.initials: H
authors.lastname: McHaourab
authors.forename: Carl Hirschie
authors.initials: CH
authors.lastname: Johnson
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005454:Fluorescence Polarization; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010455:Peptides; D010766:Phosphorylation; D011485:Protein Binding; D046940:Synechococcus / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; C527142:KAI 9803; C114269:KaiA protein, cyanobacteria; C114270:KaiB protein, cyanobacteria; C114271:KaiC protein, cyanobacteria; D010455:Peptides