May 17, 2005 | David F. Coppedge

Rotary Clock Discovered in Bacteria

What could be more mechanical than a mechanical clock?  A biochemist has discovered one in the simplest of organisms, one-celled cyanobacteria.  Examining the three complex protein components of its circadian clock, he thinks he has hit on a model that explains its structure and function: it rotates to keep time.  Though it keeps good time, this clock is only about 10 billionths of a meter tall.
    Scientists have known the parts of the cyanobacterial clock.  They are named KaiA, KaiB, and KaiC.  Jimin Wang of the Department of Molecular Biophysics and Biochemistry at Yale, publishing in Structure,1 has found an elegant solution to how the parts interact.  He was inspired by the similarity of these parts to those in ATP synthase (see 04/30/2005 entry), a universal enzyme known as a rotary motor.  Though structurally different, the Kai proteins appear to operate as another rotary motor – this time, a clock.
    We learned last time (see 09/15/2004 entry) that the parts interact in some way in sync with the diurnal cycle, but the mechanism was still a “black box.”  Wang found that the KaiC part, a six-sided hexagonal cylinder, has a central cavity where the KaiA part can fit when it undergoes an “activation” that changes its shape, somewhat like unfolding scissors.  Like a key, it fits into the central shaft and turns.  The KaiB part, like a wing nut, fastens on KaiB at the bottom of the KaiC carousel.  For every 120° turn of the spindle, phosphate groups attach to the outside of the carousel, till KaiC is fully saturated, or phosphorylated.  This apparently happens to multiple Kai complexes during the night.
    How does this keep time?  When unphosphorylated, KaiC affects the expression of genes.  During the night, when complexed with the other two parts, it is repressed from acting, effectively shutting down the cell for the night.  Apparently many of these complexes form and dissociate each cycle.  As the complexes break up in the morning, expression resumes, and the cell wakes up.  When KaiC separates from the other parts, it is destroyed, stopping its repression of genes and stimulating the creation of more KaiC.  “In summary,” he says, “the Kai complexes are a rotary clock for phosphorylation, which sets the destruction pace of the night-dominant Kai complexes and timely releases KaiA.”  The system sets up a day-night oscillation feedback loop that allows the bacterium keep in sync with the time of day.
    Wang shares the surprise that a bacterium could have a clock that persists longer than the cell-division cycle.  This means that the act of cell division does not break the clock:

The discovery of a bacterial clock unexpectedly breaks the paradigm of biological clocks, because rapid cell division and chromosome duplication in bacteria occur within one circadian period (Kondo et al., 1994 and Kondo et al., 1997).  In fact, these cyanobacterial oscillators in individual cells have a strong temporal stability with a correlation time of several months   (Emphasis added in all quotes.)

Wang’s article has elegant diagrams of the parts and how they precisely fit together.  In his model, the KaiC carousel resembles the hexagonal F1 motor of ATP synthase, and the KaiA “key” that fits into the central shaft resembles the camshaft.  KaiB, in turn, acts like the inhibitor in ATP synthase.  “The close relationship between the two systems may well extend beyond their structural similarity,” he suggests in conclusion, “because the rhythmic photosynthesis-dependent ATP generation is an important process under the Kai circadian regulation.”

1Jimin Wang, “Recent Cyanobacterial Kai Protein Structures Suggest a Rotary Clock,” Structure, Volume 13, Issue 5, May 2005, Pages 735-741, doi:10.1016/j.str.2005.02.011.

Need we tell readers what we are about to say?  “There is no mention of evolution in this paper.”  The inverse law of Darwinese stands: the more detailed the discussion of cellular complexity, the less the tendency to mention evolution.
    This is wonderful stuff.  The cell is alive with wheels, gears, motors, monorails, winches, ratchets and clocks.  Paley would be pleased.

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