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The role of partially unfolded states of proteins in biological signal transduction: Photoactive Yellow Protein and AppA

The role of partially unfolded states of proteins in biological signal transduction: Photoactive Yellow Protein and AppA

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.

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Coordinator

UNIVERSITEIT UTRECHT

Address

Heidelberglaan 8
Utrecht

Netherlands

Administrative Contact

Bas R. LEEFLANG (Dr)

Project information

Grant agreement ID: 501495

  • Start date

    1 May 2004

  • End date

    30 April 2006

Funded under:

FP6-MOBILITY

  • Overall budget:

    € 158 326

  • EU contribution

    € 158 326

Coordinated by:

UNIVERSITEIT UTRECHT

Netherlands