[tt] Physorg: Researchers better understand biological clock

[Premise Checker]

Researchers better understand biological clock
http://www.physorg.com/news111417864.html
7.10.12

Researchers at Harvard University and the Howard Hughes Medical
Institute (HHMI) have discovered that a simple circadian clock
found in some bacteria operates by the rhythmic addition and
subtraction of phosphate groups at two key locations on a single
protein. This phosphate pattern is influenced by two other
proteins, driving phosphorylation to oscillate according to a
remarkably accurate 24-hour cycle.

Writing this week in the journal Science, the scientists describe
what causes a trio of proteins, if placed in a test tube with the
common biochemical fuel ATP as a source of phosphate, to function
as a minimalist biological clock of sorts, maintaining an accurate
circadian rhythm for long periods of time.

The new Harvard work builds upon research reported in 2005 by
biologist Takao Kondo and colleagues at Nagoya University in Japan.
That team initially reported that a circadian clock could be
reconstituted in a test tube solely with three proteins and ATP.

"The most striking feature of this circadian oscillator is its
precision," says Erin K. O'Shea, professor of molecular and
cellular biology and chemistry and chemical biology in Harvard's
Faculty of Arts and Sciences (FAS), director of the FAS Center for
Systems Biology, and Howard Hughes Medical Institute investigator.
"Even in the absence of external cues -- in total darkness -- these
minuscule protein-based clocks can maintain precision to a small
fraction of a day over several weeks."

O'Shea, postdoctoral researcher Michael J. Rust, graduate student
Joseph S. Markson, and colleagues studied circadian rhythms in
cyanobacteria, better known as blue-green algae. These simple
organisms, responsible for some 70 percent of the Earth's
photosynthesis, devote most of their energies toward just two
biological processes: photosynthesis and reproduction.

The scientists scrutinized the activity of three bacterial proteins
known as KaiA, KaiB, and KaiC. They found that during the daytime,
KaiC is cyclically phosphorylated at two amino acid residues: first
at a specific threonine, and then at a specific serine. During
nighttime hours, the two amino acids are dephosphorylated in the
same order.

The KaiA protein promotes the phosphorylation of KaiC, and KaiB,
sensing one of the phosphorylated forms of KaiC, blocks KaiA's
activity, creating an intricate biochemical dance that results in a
nearly perfect 24-hour oscillation. The researchers' subsequent
mathematical analysis confirmed that this distinctive dynamic
would, in fact, reproduce a circadian period.

The bacterial proteins studied by O'Shea, Rust, Markson, and
colleagues are not known to exist in humans, but the researchers
say their findings illuminate general feedback mechanisms that
could serve to establish chronological oscillations in a whole host
of organisms.

"It's unknown whether such a mechanism is at the core of all
circadian clocks," says Rust, a postdoctoral researcher in
Harvard's Department of Molecular and Cellular Biology. "It's the
simplest chemical oscillator known, and we are looking at it as a
possible model for other species."

O'Shea says the 2005 finding by Kondo and colleagues that a
cyanobacterial circadian clock could be recreated in a test tube
using only three proteins and ATP surprised researchers because it
showed that some circadian rhythms are driven solely by
protein-protein interactions.

"It demonstrated that circadian clocks can operate independently of
DNA and most cellular components, contradicting the previous
prevailing theory that an entire organism was likely needed to
maintain a clock," she says.

O'Shea, Rust, and Markson's co-authors are William S. Lane at
Harvard and Daniel S. Fisher at Stanford University. The research
was sponsored by HHMI and the National Science Foundation.

Source: Harvard University