title: Crystal structure of the redox-active cofactor dibromothymoquinone bound to circadian clock protein KaiA and structural basis for dibromothymoquinone's ability to prevent stimulation of KaiC phosphorylation by KaiA.
abstract: KaiA protein that stimulates KaiC phosphorylation in the cyanobacterial circadian clock was recently shown to be destabilized by dibromothymoquinone (DBMIB), thus revealing KaiA as a sensor of the plastoquinone (PQ) redox state and suggesting an indirect control of the clock by light through PQ redox changes. Here we show using X-ray crystallography that several DBMIBs are bound to KaiA dimer. Some binding modes are consistent with oligomerization of N-terminal KaiA pseudoreceiver domains and/or reduced interdomain flexibility. DBMIB bound to the C-terminal KaiA (C-KaiA) domain and limited stimulation of KaiC kinase activity by C-KaiA in the presence of DBMIB demonstrate that the cofactor may weakly inhibit KaiA-KaiC binding.
authors.affiliation: Department of Biochemistry, Vanderbilt University, School of Medicine, Nashville, TN 37232, USA.
authors.forename: Rekha
authors.initials: R
authors.lastname: Pattanayek
authors.forename: Said K
authors.initials: SK
authors.lastname: Sidiqi
authors.forename: Martin
authors.initials: M
authors.lastname: Egli
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003991:Dibromothymoquinone / Q000737:chemistry*; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; C114269:KaiA protein, cyanobacteria; C114271:KaiC protein, cyanobacteria; D003991:Dibromothymoquinone