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Content archived on 2024-05-07

An integrated methodological approach to structural studies on complexes of GTP-binding proteins with their effectors and regulators and design of new molecules

Objective



The project concerns the elucidation of the structures of complexes of Ras-related GTP-binding proteins with their effectors and regulators. It is a multi-disciplinary, multi-national approach which brings together biochemists, NMR spectroscopists, X-ray crystallographers and modellers all of which are crucial for an efficient structural biology programme. The network intends to develop methods for the identification and recombinant expression of proteins, for the NMR spectroscopy of larger proteins and complexes and for combining NMR spectroscopy with X-ray crystallography. These methods will be applied to identify and express complexes of Ras, Ral, Rap, Rac and Rho and to solve their three-dimensional structures by NMR and X-ray crystallography. The structural data will be used for the analysis of the protein-protein interfaces and to derive common principles. The structural, biochemical and biophysical results will aid in the understanding of the function of Ras-related switch proteins and the signalling cascades they control. It will also lead to an understanding of the specificity of these processes at the atomic level. The structural analysis of the protein-protein interactions will lead to the design of new types of GTP-binding proteins and their partners which can be analysed in the cell. It will also provide a structural basis for the design and/or improvement of drugs directed against the function of these proteins, since they are involved in the control of number of diseases. The knowledge obtained will also be used to screen for hitherto unknown interacting molecules in the databases of large-scale sequencing projects. Finally, the development of NMR techniques will be incorporated into software packages that are sold by the commercial participant of the network.

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Call for proposal

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.
EU contribution
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Address
201,Otto-Hahn-Strasse 11
44227 DORTMUND
Germany

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Total cost
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Participants (5)