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dc.contributor.authorManahan, Craig
dc.date.accessioned2016-04-04T18:05:00Z
dc.date.available2021-02-01T07:00:39Z
dc.date.issued2016-02-01
dc.identifier.otherbibid: 9596974
dc.identifier.urihttps://hdl.handle.net/1813/43574
dc.description.abstractThe circadian clock is necessary throughout almost all life forms in order to control physiological changes throughout the ~24 hour day. At the molecular level, a transcription-translation feedback loop is the foundation for eukaryotic clocks, and this loop is entrained by external cues to the change in environment. In this study, both the positive arm of the loop and the method of entrainment by light have been investigated for proteins involved in the circadian clock of the fruit fly Drosophila melanogaster. Cycle (CYC) is a transcription factor that dimerizes with its partner Clock (dCLK) through two tandem Per-ARNT-Sim domains to activate clock controlled genes. In this study, the structure of the PAS B domain of Cycle was investigated by crystallography, and the behavior of this domain was investigated. We reveal by comparing the solved structure with that of homologous mammalian protein mBMAL1 what structural changes occur upon binding of partner CLK, and we point out differences in the structure between CYC and mBMAL1. We show the importance of a tryptophan residue in mediating homodimerizion of CYC and heterodimerization of CYC with CLK and Period (PER). We also discover a novel glycerol binding mode in CYC, and discuss possible roles for this binding. Cryptochrome (CRY) provides the major light entrainment mechanism in Drosophila by using light to alter conformation, bind partners Timeless (TIM) and Jetlag (JET), and lead to their degradation. In this study we investigate how CRY senses light mechanistically by reducing its FAD cofactor, whether this reduction is sufficient to lead to partner binding, and why FAD reduction causes conformational changes.
dc.language.isoen_US
dc.titleStructure And Reactivity Of Cycle And Cryptochrome: Two Key Components Of The Drosophila Circadian Clock
dc.typedissertation or thesis
thesis.degree.disciplineChemistry and Chemical Biology
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Chemistry and Chemical Biology
dc.contributor.chairCrane,Brian
dc.contributor.committeeMemberCerione,Richard A
dc.contributor.committeeMemberLin,Hening


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