Rotary Clock Discovered in Bacteria 05/17/2005 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, 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 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.
[2005/05/17] Rotary Clock Discovered in Bacteria
