SFB 860: Integrative Structural Biology of Dynamic Macromolecular Assemblies

大分子组合的动力学是一种基本性质，对其分子和细胞功能有重要影响。合作研究中心分析了几个大型大分子复合物的动力学，包括它们的结构、它们的构象和组成的变化、它们与其他生物大分子的相互作用以及它们在细胞中的时间和空间位置。因此，合作研究中心的项目集中于三维结构的确定，结构对分子和细胞功能的影响的推断，组装，重塑和拆卸过程中的动态过程，天然展开结构域的作用，翻译后修饰对结构，功能和动力学的影响，功能复合物及其亚基的构象动力学。以及大分子相互作用的动力学和热力学。由于大型多蛋白和核糖核蛋白复合物的惊人复杂性，经典的生化、生物物理和结构测定方法-当专门使用时-不能满足详细理解此类系统的要求。在以前的资助期间，中心为样品制备、大分子相互作用网络的鉴定以及成分和结构动力学分析等方面的最先进战略建立了框架。结合单粒子电子显微镜、晶体学、核磁共振波谱学、小角度x射线散射、单分子技术和计算工具的混合方法被应用于生成大型大分子复合物的可测试原子模型。合作研究中心在Göttingen中整合了广泛的跨学科能力，用于综合分析一系列确定的大分子复合物，如剪接体、核糖体、RNA聚合酶II及其中介复合物、线粒体转位酶复合物、核输出复合物、核孔复合物、自噬体、slp组装的信号体、COP9信号体和中间细丝。由于这些功能不同的大分子组装的挑战和方法非常相似，因此互补的生物物理和生化方法的应用，以及实验经验和专有技术的交流，为本CRC的每个项目带来了显著的附加价值。

The dynamics of large macromolecular assemblies is a fundamental property with great impact on their molecular and cellular functions. The Collaborative Research Centre analyses the dynamics of several large macromolecular complexes in respect to their structures, their changes in conformation and composition, their interactions with other biological macromolecules and with respect to their temporal and spatial location in the cell. Hence, the projects of the Collaborative Research Centre focus on the determination of three-dimensional structures, the deduction of structure’s implication for the molecular and cellular function, the dynamic processes during assembly, remodelling and disassembly, the role of natively unfolded domains, the impact of posttranslational modifications on structure, function and dynamics, the conformational dynamics of functional complexes and their subunits, and kinetics and thermodynamics of macromolecular interactions. Due to the stunning complexity of large multi-protein- and ribonucleoprotein complexes, classical biochemical, biophysical and structure determination methods - when used exclusively - do not meet the requirements to comprehend such systems in detail. During the previous funding periods the CRC has set up the framework for state-of-the-art strategies in sample preparation, identification of macromolecular interaction networks, as well as for the analysis of compositional and structural dynamics. Hybrid approaches that combine single particle electron microscopy, crystallography, NMR spectroscopy, small angle X-ray scattering, single-molecule techniques and computational tools are applied to generate testable atomic models of large macromolecular complexes. The Collaborative Research Centre bundles a wide spectrum of interdisciplinary competences present in Göttingen for the integrative analysis of a defined set of large macromolecular complexes, like the spliceosome, the ribosome, the RNA polymerase II and its Mediator complex, the mitochondrial translocase complex, nuclear export complexes, the nuclear pore complex, the autophagosome, SLP-assembled signalosomes, the COP9 signalosome, and intermediate filaments. Since the challenges and approaches are very similar for these functionally different macro¬molecular assemblies, the application of complementary biophysical and biochemical methods, as well as the exchange of experimental experiences and know-how results in a significant added value for each project of this CRC.