SFB 860: Integrative Structural Biology of Dynamic Macromolecular Assemblies

SFB 860：动态大分子组装的综合结构生物学

• 批准号: 105286809
• 金额: --
• 依托单位: Georg-August-Universität Göttingen
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/105286809?language=en
• 关键词: SFB; 860; Integrative; Structural; Biology

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.

大分子组装体的动力学性质是其分子和细胞功能的重要基础。该合作研究中心分析了几种大分子复合物的结构、构象和组成变化、与其他生物大分子的相互作用以及它们在细胞中的时空位置等方面的动态。因此，合作研究中心的项目集中在三维结构的确定，结构对分子和细胞功能的影响的推导，组装，重塑和拆卸过程中的动态过程，天然未折叠结构域的作用，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。由于大的多蛋白质和核糖核蛋白复合物的惊人的复杂性，经典的生物化学，生物物理和结构测定方法-当专门使用时-不满足详细理解这样的系统的要求。在之前的资助期间，CRC已经建立了样品制备，大分子相互作用网络识别以及成分和结构动态分析的最先进策略的框架。混合的方法，结合联合收割机单粒子电子显微镜，晶体学，核磁共振光谱，小角X射线散射，单分子技术和计算工具，应用于产生可测试的大分子复合物的原子模型。合作研究中心捆绑了广泛的跨学科能力，目前在哥廷根的一组定义的大分子复合物的综合分析，如剪接体，核糖体，RNA聚合酶II及其介体复合物，线粒体转位酶复合物，核出口复合物，核孔复合物，自噬体，SLP组装信号体，COP9信号体和中间丝。由于这些功能不同的大分子组装体面临的挑战和方法非常相似，因此互补的生物物理和生物化学方法的应用以及实验经验和专有技术的交流为该CRC的每个项目带来了显著的附加值。