HumanRib: metal ion binding - stucture - function .. (HumanRib)
HumanRib: metal ion binding - stucture - function relations of the human CPEB3 ribozyme
Date du début: 1 oct. 2013,
Date de fin: 31 mars 2015
Until recently, ribozymes (enzymes composed of folded RNA) were found only in lower organisms. The discovery of the human CPEB3 ribozyme, related to the Hepatitis Delta Virus one, was an enormous breakthrough, which gave rise to numerous scientific questions.In the scope of this project, I want to answer the most emerging ones; I aim to solve the NMR structure of the whole CPEB3 ribozyme (we already have some promising preliminary results), as well as to crystallize it (in collaboration with another group) and compare the solution NMR and solid state X-ray structure. To understand changes in dynamics and folding of the ribozyme in the presence of Mg(II) (the natural cofactor), and also in the presence of other metal ions, single-molecule FRET (Förster Resonance Energy Transfer) experiments will be performed. As a long–term goal (after the repatriation to my home University), I will use NMR to characterize specific metal binding sites, structural and thermodynamic changes within the ribozyme upon the addition of metal ions.A big advantage of this project is that the ribozyme will be studied as a whole unit and not cut down into smaller parts. Although much more challenging, this will give a complete and clear view on the metal ion binding - structure - function relations.I am convinced that the proposed interdisciplinary project, which combines structural biology with coordination chemistry, is an exciting and necessary field of study, crucial for understanding not only the complicated structure and pathway of metal – mediated cleavage of the only known human ribozyme, but also for providing insight into its evolutional background, after being compared to the mechanism in which the viral HDV ribozyme functions.
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