Research program

Summary

A fundamental property of large macromolecular assemblies is their dynamics, which has great impact on their molecular and cellular functions. This CRC analyses the dynamics of several large macromolecular complexes with 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 CRC focus on the determination of three-dimensional structures, the deduction of the 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, as well as kinetics and thermodynamics of macromolecular interactions. Studying the three-dimensional structure and the dynamics of single, average-size proteins is nowadays mostly 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 bundles 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 the challenges and approaches are very similar for these functionally different macro­molecular 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.

 

The CRC 860 has been strengthening a collaborative framework comprising biochemists and cell biologists studying the function of large macromolecular assemblies, as well as structural biologists and biophysicists in order to perform integrative studies on the structure, dynamics and function of large macromolecular assemblies. During the first funding period significant progress has been achieved with respect to the goals of the CRC. The outcome of the work within the CRC projects has led to 97 publications in peer review journals. Most importantly, 32 of these papers are joined publications with contributions from two ore more CRC research groups. In addition to these joined publications related to the CRC projects, members of CRC published yet another 48 joint papers that are not related to the CRC projects. This clearly demonstrates the high degree of close collaborations and joint efforts between the CRC groups.