Fig. 8.

Model for LDC sensitivity due to circadian clock disfunction. (A) Conventionally, the role of KaiA is primarily to bind to the A-loops of the CII domain of KaiC, stimulating its autophosphorylation and consequently increasing the activity of the kinase SasA; this activity in turn results in accumulation of phosphorylated RpaA throughout the day. P-RpaA initiates the expression of circadian-controlled nighttime class 1 genes at dusk. Yellow and red dots on KaiC represent phosphorylation at S431 and T432, respectively. A red dot also represents phosphorylation on RpaA. The rare fold switch of KaiB is represented by different orange shapes. The major conformational change of KaiA bound to the CII A-loops versus the KaiB ring and the exposure of the KaiB binding site on the CI ring of KaiC are also depicted. (B) Without KaiA, KaiC phosphorylation is suppressed and, thus, SasA kinase activity is diminished, reducing the pools of SasA-mediated P-RpaA. A small fraction of the KaiC pool that is phosphorylated even in the absence of KaiA can bind KaiB. CikA has access to these KaiC-bound KaiB proteins that are usually occupied by KaiA and becomes hyperactive; excessive CikA phosphatase activity extinguishes intracellular pools of P-RpaA and eliminates the cell’s ability to express genes needed for survival in LDC. Modified from ref. 11, with permission from AAAS. The dotted line in the B graph represents the WT levels of P-RpaA from A.