PER:PER Protein Pair Required For Circadian Clock Function

Scientists from Queen Mary, University of London have discovered a new
protein complex operating in fruit fly circadian clocks, which may also
help to
regulate our own biological clocks.



Circadian clocks are thought to have evolved to enable organisms to match
their behaviour to specific time slots during the 24 hour day. They are
synchronised with our surrounding environment via natural light or
temperature cycles.



Professor Ralf Stanewsky and his team from Queen Mary's School of
Biological and Chemical Sciences study the circadian clocks of Drosophila,
a type
of fruit fly. The flies' body-clocks are regulated by two proteins called
Period (PER) and Timeless (TIM).



The current model of circadian clocks in flies involves the formation of
complexes between these two different clock proteins, known as
heterodimers
(TIM:PER). Similarly, mammalian circadian clocks (including those in
humans) also rely on a heterodimer complex made up of the Period (PER) and
Cryptochrome (CRY) proteins.



But now, a new study performed in Professor Stanewsky's lab shows that a
complex made of two identical Period proteins, known as a PER:PER
homodimer
is also crucial for circadian clock function in flies. Writing in the
journal PLoS Biology, Stanewsky explains how his team designed a PER
protein
which could only join with TIM, not with itself.



"We generated a mutation in the PER protein which prevented the formation
of the PER:PER dimer, but not that of the PER:TIM heterodimer," he
explains. "These mutant flies showed drastically impaired behaviour and
molecular clock function, suggesting that PER homodimers are vital for the
function of circadian clocks."

The mutant fly PER proteins were designed using structural protein data
generated by Dr. Eva Wolf at the MPI in Dortmund (Germany). In the same
issue
of PLoS Biology the Wolf group reports findings indicating that the
PER:PER homodimer could also be an important feature of circadian clocks
in
mammals, including humans.



Funding - Our work is supported by Entrainment of the Circadian Clock
(EUCLOCK), an Integrated Project (framework 6) of the EU. KFC is supported
by a
Studentship from Queen Mary College and EW is supported by a grant of the
Deutsche Forschungsgemeinschaft (WO-695/4).



Competing interests statement - The authors declare that no competing
interests exist.



Citation:

"A role for the PERIOD:PERIOD homodimer in the Drosophila circadian clock."
Landskron J, Chen KF, Wolf E, Stanewsky R (2009)

PLoS Biol 7(4): e1000003. doi:10.1371/journal.pbio.1000003


Source
Plos Biology