SFB 860: Integrative Structural Biology of Dynamic Macromolecular Assemblies

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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.