3gec
From Proteopedia
Crystal structure of a tandem PAS domain fragment of Drosophila PERIOD
Structural highlights
Function[PER_DROME] Essential for biological clock functions. Determines the period length of circadian and ultradian rhythms; an increase in PER dosage leads to shortened circadian rhythms and a decrease leads to lengthened circadian rhythms. Essential for the circadian rhythmicity of locomotor activity, eclosion behavior, and for the rhythmic component of the male courtship song that originates in the thoracic nervous system. The biological cycle depends on the rhythmic formation and nuclear localization of the TIM-PER complex. Light induces the degradation of TIM, which promotes elimination of PER. Nuclear activity of the heterodimer coordinatively regulates PER and TIM transcription through a negative feedback loop. Behaves as a negative element in circadian transcriptional loop. Does not appear to bind DNA, suggesting indirect transcriptional inhibition. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPERIOD proteins are central components of the Drosophila and mammalian circadian clocks. The crystal structure of a Drosophila PERIOD (dPER) fragment comprising two PER-ARNT-SIM (PAS) domains (PAS-A and PAS-B) and two additional C-terminal alpha-helices (alphaE and alphaF) has revealed a homodimer mediated by intermolecular interactions of PAS-A with tryptophane 482 in PAS-B and helix alphaF. Here we present the crystal structure of a monomeric PAS domain fragment of dPER lacking the alphaF helix. Moreover, we have solved the crystal structure of a PAS domain fragment of the mouse PERIOD homologue mPER2. The mPER2 structure shows a different dimer interface than dPER, which is stabilized by interactions of the PAS-B beta-sheet surface including tryptophane 419 (equivalent to Trp482dPER). We have validated and quantitatively analysed the homodimer interactions of dPER and mPER2 by site-directed mutagenesis using analytical gel filtration, analytical ultracentrifugation, and co-immunoprecipitation experiments. Furthermore we show, by yeast-two-hybrid experiments, that the PAS-B beta-sheet surface of dPER mediates interactions with TIMELESS (dTIM). Our study reveals quantitative and qualitative differences between the homodimeric PAS domain interactions of dPER and its mammalian homologue mPER2. In addition, we identify the PAS-B beta-sheet surface as a versatile interaction site mediating mPER2 homodimerization in the mammalian system and dPER-dTIM heterodimer formation in the Drosophila system. Structural and functional analyses of PAS domain interactions of the clock proteins Drosophila PERIOD and mouse PERIOD2.,Hennig S, Strauss HM, Vanselow K, Yildiz O, Schulze S, Arens J, Kramer A, Wolf E PLoS Biol. 2009 Apr 28;7(4):e94. PMID:19402751[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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