title: Crystal structure and interactions of the PAS repeat region of the Drosophila clock protein PERIOD.
abstract: 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 alpha helices (alphaE and alphaF). Our analysis reveals a noncrystallographic dPER dimer mediated by intermolecular interactions of PAS-A with PAS-B and helix alphaF. We show that alphaF is essential for dPER homodimerization and that the PAS-A-alphaF interaction plays a crucial role in dPER clock function, as it is affected by the 29 hr long-period perL mutation.
authors.affiliation: Department of Structural Biology, Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
authors.forename: Ozkan
authors.initials: O
authors.lastname: Yildiz
authors.forename: Masao
authors.initials: M
authors.lastname: Doi
authors.forename: Irene
authors.initials: I
authors.lastname: Yujnovsky
authors.forename: Luca
authors.initials: L
authors.lastname: Cardone
authors.forename: Alex
authors.initials: A
authors.lastname: Berndt
authors.forename: Sven
authors.initials: S
authors.lastname: Hennig
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schulze
authors.forename: Claus
authors.initials: C
authors.lastname: Urbanke
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
authors.forename: Eva
authors.initials: E
authors.lastname: Wolf
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002940:Circadian Rhythm; D018360:Crystallography, X-Ray; D019281:Dimerization; D004330:Drosophila / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D056950:Period Circadian Proteins; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins