Objective Partially unfolded and/or molten-globule like states are known to play an important role in vitro, in particular for photoreceptor-mediated signalling. It has been reported that this intrinsically unstructured state offers important advantages; however for a better understanding of this phenomena, structural information about unfolded states of proteins is crucial. The aim of this project is to increase understanding of the functional role of partially unfolded states of proteins that are involved in biological transudation. This will be achieved by characterizing the structure and interactions of these states in the model system PYP (Photoactive Yellow Protein). This system is involved in designating pathway of a cryptozoic light receptor, which is believed to mediate negative photo taxis in certainhalophilic bacteria. The methods to be developed for characterizing these states will then be applied to theflavoprotein Appal, a recently discovered photoreceptor protein from Rib. Sphaeroides. The main experimental technique that will be employed is high-resolution NMR spectroscopy, in combination with computational tools, based on the Molecular Dynamics approach. They will be developed to describe the ensemble of conformers that constitute a (partially) molten globule state of a protein. These tools will have important implications for the more general questions surrounding (functional) protein folding and unfolding. Folding is thought to be involved in human pathologies such as Alzheimer disease and Creutzfeldt-Jakobdisease. Since the interaction partners are known for the Appal photoreceptor protein, this for the first time allows the complete reconstitution of the in vivo signal transudation chain, initiated by Appal. Fields of science medical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesphysical sciencesopticsspectroscopyabsorption spectroscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingmedical and health sciencesbasic medicinepathology Keywords AppA NMR spectroscopy PYP Photoactive Yellow Protein computational tools flavoprotein molecular modeling photoreceptors protein folding transient intermediates Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2002-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator UNIVERSITEIT UTRECHT Address Heidelberglaan 8 Utrecht Netherlands See on map EU contribution € 0,00
