SFB 610: Variation in Protein Conformation: Cellbiological and Pathological Relevance

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The knowledge of protein conformation on a molecular level is of great relevance to our overall understanding of cellular mechanisms. Divergent conformations of proteins can be obtained by different folding, by different post translational modifications, but also by different interactions with biomolecular partners. In this project protein conformations shall be characterized by using aptamers (RNA molecules with specific binding properties), peptides or by means of molecular biological techniques, and analyzed by NMR, X-ray analysis or molecular modelling. The major targets either focus on proteins with conformation relevant for basic cellular activies like receptors, peptide ligases or adhesion molecules, or with protein conformations that play a role in diseases. These include heterochromatin proteins (multiple myeloma), the Tau-protein (Alzheimer disease) or poly(A)-binding proteins (oculopharyngeale muscledystrophy). Furthermore therapeutic strategies are investigated in which protein conformations shall be addressed. By using aptamers, peptides or virosomes e.g. association of matrixmetalloprotease and TIMP or viral protein cell interactions shall be inhibited. Any successful therapies of diseases based on pathological protein conformations rely on the molecular understanding of the principles. Only a big interdisciplinary research cooperation on the borderline of basic and applied biomedical research will be able to contribute and solve these problems.