CIRCADIAN RHYTHMS - Cyanobacteria - page 318

Figure 4: Depicted is a representation of the mathematical model for phosphorylation cycle of a KaiC hexamer and its
association with KaiA and KaiB. A KaiC monomer is shown as a double circle that forms a hexamer that can associate/
dissociate with KaiA and/or KaiB. KaiC hexamers are depicted in both their default status (light blue color) and in an
altered KaiC* state that has undergone a conformational change (darker blue color). Red dots are phosphates attached to
phosphorylation sites on KaiC (residues T426, S431 and T432). KaiC hexamers can exchange monomers between hexamers
in any of the states, depicted by the double-headed arrows in the central region of the fi gure. The relative rates of exchange
between these states are illustrated by the type of double-headed arrows (thick line = high rate; thin line = medium rate;
and dashed line = low rate). With the kind permission of C. H. Johnson, Department of Biological Sciences, Vanderbilt
University, Nashville, Tennessee, USA [Mori et al . (2007) PLoS Biol 5(4): e93. doi:10.1371/journal.pbio.0050093] doi:10.1371/
journal.pbio.0050093.g003.
Color image of this figure appears in the color plate section at the end of the topic.
the built up of S-KaiC caused complete inactivation of KaiA. This led to dephosphorylation of T-KaiC
and ST-KaiC due to which S-KaiC remained as the dominant form. Lastly, when dephosphorylation of
enough S-KaiC had occurred then the activity of KaiA returned to normal and the cyclical formation
of the four forms of KaiC took place (Rust et al ., 2007). Additional support for this has been provided
by Li et al . (2009) who advocated that Thr432 constitutes the regulator for the oscillation amplitude
while Ser431 serves as the major phase regulator. These dual phosphorylation sites on KaiC thus
coordinate and control phosphorylation period. On the other hand, the importance of Thr426 to
control KaiC phosphorylation status in vitro and in vivo has been emphasized by Xu et al . (2009)
who adduced mutational and biochemical evidences in support of their conclusions. A change in
Ser431 and Thr432 by way of site-directed mutagenesis or due to an inhibition of phosphorylation
then Thr426 is liable to undergo phosphorylation. Kim et al . (2008) studied the nature of KaiA
binding sites on KaiC (C KABD1 and C KABD2 ) in the C-terminal loops (termed by them as A-loops).