Structure of the N-terminal domain of the circadian clock-associated histidine kinase SasA.
Circadian oscillators are endogenous biological systems that generate the approximately 24 hour temporal pattern of biological processes and confer a reproductive fitness advantage to their hosts. The cyanobacterial clock is the simplest known and the only clock system for which structural information for core component proteins, in this case KaiA, KaiB and KaiC, is available. SasA, a clock-associated histidine kinase, is necessary for robustness of the circadian rhythm of gene expression and implicated in clock output. The N-terminal domain of SasA (N-SasA) interacts directly with KaiC and likely functions as the sensory domain controlling the SasA histidine kinase activity. N-SasA and KaiB share significant sequence similarity and, thus, it has been proposed that they would be structurally similar and may even compete for KaiC binding. Here, we report the NMR structure of N-SasA and show it to be different from that of KaiB. The structural comparisons provide no clear details to suggest competition of SasA and KaiB for KaiC binding. N-SasA adopts a canonical thioredoxin fold but lacks the catalytic cysteine residues. A patch of conserved, solvent-exposed residues is found near the canonical thioredoxin active site. We suggest that this surface is used by N-SasA for protein-protein interactions. Our analysis suggests that the structural differences between N-SasA and KaiB are the result of only a few critical amino acid substitutions.
Department of Biochemistry and Biophysics, Texas A&M University, College Station 77843, USA.
Ioannis
I
Vakonakis
Douglas A
DA
Klewer
Stanly B
SB
Williams
Susan S
SS
Golden
Andy C
AC
LiWang
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001683:Biological Clocks; D002940:Circadian Rhythm; D056925:Circadian Rhythm Signaling Peptides and Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010770:Phosphotransferases / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; C114270:KaiB protein, cyanobacteria; C114271:KaiC protein, cyanobacteria; D010770:Phosphotransferases; C083143:SasA protein, Synechococcus