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

分子水平上的蛋白质构象知识与我们对细胞机制的整体理解有很大关系。蛋白质的不同构象可以通过不同的折叠、不同的翻译后修饰，以及与生物分子伴侣的不同相互作用来获得。在本项目中，应使用适体（具有特异性结合特性的RNA分子）、肽或通过分子生物学技术表征蛋白质构象，并通过NMR、X射线分析或分子建模进行分析。主要靶点集中在与基本细胞活性相关的构象的蛋白质，如受体、肽连接酶或粘附分子，或在疾病中起作用的蛋白质构象。这些包括异染色质蛋白（多发性骨髓瘤）、Tau蛋白（阿尔茨海默病）或多聚腺苷酸结合蛋白（眼咽肌营养不良）。此外，治疗策略的研究，其中蛋白质构象应解决。通过使用适体、肽或病毒体，例如基质金属蛋白酶和TIMP或病毒蛋白的结合，细胞相互作用应被抑制。任何基于病理性蛋白质构象的疾病的成功疗法都依赖于对原理的分子理解。只有在基础生物医学研究和应用生物医学研究的边界上进行大的跨学科研究合作，才能为解决这些问题做出贡献。

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.