SFB 860:  Integrative Structural Biology of Dynamic Macromolecular Assemblies

• Subject Area: Biology
• Term: from 2010 to 2022
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 105286809

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.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Structural dynamics of the yeast spliceosome during its activation and catalysis of splicing (Project Head Lührmann, Reinhard )
• A02 - Crystallographic studies on molecular motors of the spliceosome (Project Head Ficner, Ralf )
• A03 - Ribosome dynamics in translation (Project Head Rodnina, Marina V. )
• A04 - Dynamics of single ribosomes probed with atomic force microscopy (Project Head Schaap, Iwan )
• A05 - High-resolution structure determination of dynamic macromolecular complexes by cryo-EM (Project Head Stark, Holger )
• A06 - Single-molecule fluorescence spectroscopy and imaging of the structure and dynamics of macromolecular assemblies (Project Head Enderlein, Jörg )
• A07 - Interactions of the essential RNase Y in Bacillus subtilis (Project Head Stülke, Jörg )
• A09 - Structural and functional dynamics of slam RNA-protein particles in Drosophila embryos (Project Head Großhans, Jörg )
• A10 - Protein cross-linking of macromolecular complexes (Project Head Urlaub, Henning )
• A11 - Molecular mechanisms and complex formation in the cytoplasmic mRNA quality control (Project Head Krebber, Heike )
• A12 - RNA elements and protein factors required for pre-ribosome remodelling during 60S biogenesis in yeast (Project Head Bohnsack, Markus T. )
• A13 - Integrated structural biology of the Mediator complex (Project Head Cramer, Patrick )
• A14 - Translation termination in human mitochondria: Why do we need four release factors? (Project Head Richter-Dennerlein, Ricarda )
• A15 - Scanning dynamics of the mammalian ribosome during translation initiation (Project Head Adio, Sarah )
• A16 - Molecular dynamics simulations of protein-nucleotide interaction (Project Head Hub, Jochen )
• B01 - Structure and dynamics of the mitochondrial presequence translocase (Project Head Rehling, Peter )
• B02 - Coupled binding and folding in protein assemblies (Project Head Zweckstetter, Markus )
• B03 - X-ray crystallography, biochemistry, nuclear transport (Project Heads Ficner, Ralf ;  Görlich, Dirk )
• B04 - Structure and molecular function of the WD-40 repeat containing autophagy proteins Atg18, Atg21 and Hsv2 (Project Heads Ficner, Ralf ;  Kühnel, Karin ;  Thumm, Michael )
• B05 - Assembly and activation of multimolecular signaling clusters in B lymphocytes (Project Heads Griesinger, Christian ;  Wienands, Jürgen )
• B06 - Dynamics of the fungal COP9 signalosome and LID MPN/PCI complexes (Project Head Braus, Gerhard H. )
• B07 - Molecular mechanism, structural organisation and dynamics of the pyruvate dehydrogenase multienzyme complex (Project Head Tittmann, Kai )
• B08 - Structure-function analysis of nuclear export complexes and their interaction with nucleoporins (Project Heads Ficner, Ralf ;  Kehlenbach, Ralph )
• B09 - Computational methods for modeling macromolecular complexes (Project Head Habeck, Michael )
• B10 - The role of phosphorylations in intermediate filament assembly and disassembly (Project Head Köster, Sarah )
• B11 - Structure and dynamics of the NPC permeability barrier (Project Heads Andreas, Loren ;  Görlich, Dirk )
• Z01 - Crystallization Facility (Project Head Ficner, Ralf )
• Z02 - Central Tasks (Project Head Ficner, Ralf )

• Applicant Institution: Georg-August-Universität Göttingen
• Participating Institution: Max-Planck-Institut für biophysikalische Chemie; (Karl-Friedrich-Bonhoeffer-Institut) (aufgelöst); Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE); Standort Göttingen
• Spokesperson: Professor Dr. Ralf Ficner