Introduction of SFB860

The dynamics of large macromolecular assemblies is a fundamental property that has great impact on their molecular and cellular function. This CRC will analyze the dynamics of several large macromolecular complexes with regard 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 CRC 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. Studying the three-dimensional structure and the dynamics of single, average-size proteins is nowadays mostly a routine. However, 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. Innovative strategies have to be developed for 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 required to generate testable atomic models of large macromolecular complexes. The CRC will bundle a wide spectrum of interdisciplinary competences present in Göttingen for the integrative analysis of a defined set of large macromolecular complexes, namely the spliceosome, the ribosome, the RNA degradosome, the mRNP locasome, the slam RNP, the mitochondrial translocase complex, nuclear export complexes, autophagy protein complexes, SLP-assembled signalosomes, the COP9 signalosome and the pyruvate dehydrogenase mulitenzyme complex. Since 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 will result in a significant added value for each project.