PERIOD proteins are central components of the Drosophila and mammalian circadian clock. Their function is controlled by daily changes in synthesis, cellular localization, phosphorylation, degradation, as well as specific interactions with other clock components. Here we present the crystal structure of a Drosophila PERIOD (dPER) fragment comprising two tandemly organized PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B) and two additional C-terminal α helices (αE and αF). Our analysis reveals a noncrystallographic dPER dimer mediated by intermolecular interactions of PAS-A with PAS-B and helix αF. We show that αF is essential for dPER homodimerization and that the PAS-A-αF interaction plays a crucial role in dPER clock function, as it is affected by the 29 hr long-period perL mutation.
ASJC Scopus subject areas
- Molecular Biology