SFB 1381:  Dynamic organization of cellular protein machineries: From biogenesis and modular assembly to function

• Subject Area: Biology
• Term: since 2019
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 403222702

Complex biological functions are performed by multiprotein assemblies that act as molecular machineries. Their functions encompass all aspects of cellular physiology from DNA replication, repair and transcription to protein translation, folding and degradation, the conversion of energy and the transport of molecules, to the communication via signal transduction between organelles and cells. While technological advancements resulted in the identification of a plethora of different subunits and protein-protein interactions, the challenge remains to identify the step-wise assembly of the individual subunits into macromolecular complexes and the functional gain that these assemblies provide that is far more than the sum of their individual proteins. In addition, protein machineries are not static entities, but can dynamically associate with other complexes to form a network of assemblies. They can also partially or fully disassemble in response to binding of ligands or second messengers or changes within the metabolic state of the cell. In the CRC1381 we aim to address the challenging open questions of the dynamic organization of protein machineries. Our interdisciplinary approach combines molecular and cell biology, biophysics, and structural biology and enables us to comprehensively analyze the biogenesis and assembly of complex protein machineries on the molecular level up to the investigation of the functional outputs and regulatory controls that cellular demands exert on them. With this unique expertise the CRC1381 investigates i) how multiprotein machineries are assembled into functional units during biogene-sis, ii) how modular assemblies impact on function and iii) how these assemblies are integrated into dynamic cellular networks and controlled by external stimuli to adapt the cell to cellular demands. In the first funding period we generated detailed molecular insights into the composition of the investigated machineries: We uncovered missing protein components and identified novel subassemblies that mediate different functional outputs. In the second funding period we want to expand our molecular and mechanistic analysis towards integration of cellular dynamics and cellular signaling to investigate the assembled protein machineries and their different modules in the spatial and temporal cellular context. For this we will combine our core expertise with advanced microscopy techniques to address the questions how submodules are formed dynamically and at different localizations in the cell, how assembly and disassembly is regulated by signaling pathways, and how cellular protein machineries adapt their function to changes in cellular states. Building on our multidisciplinary expertise, we propose a comprehensive, and highly integrative research approach to uncover the mechanisms in biogenesis and function of multiprotein assemblies that govern the cellular processes of life.

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - Dynamic assembly, localization and rotation of the archaellum (Project Head Albers, Sonja Verena )
• A02 - Light-dependent dynamics in the assembly of the cyanobacterial motility machinery (Project Head Wilde, Annegret )
• A03 - The bacterial electron-bifurcating benzoyl-CoA reductase complex and its dynamic interaction partners (Project Head Boll, Matthias )
• A04 - Maturase assemblies in cytochrome c biogenesis (Project Head Einsle, Oliver )
• A05 - Assembly and biogenesis of respiratory complex III and of related supercomplexes (Project Head Hunte, Carola )
• A06 - Regulation of biogenesis and function of the mitochondrial protein import machinery by phosphorylation (Project Heads Köhn, Maja ;  Meisinger, Chris )
• A07 - Modular organisation of the machinery for membrane insertion of mitochondrial beta-barrel proteins (Project Head Wiedemann, Nils )
• A09 - Assembly of the T cell receptor signalosomes (Project Head Schamel, Wolfgang )
• B02 - Assembly, dynamics and function of ELAV protein machineries in neurons (Project Head Hilgers, Valerie )
• B03 - Identification and characterization of MOF interaction and substrate repertoire (Project Head Akhtar, Ph.D., Asifa )
• B04 - Diverse functions of the mitochondrial presequence processing machinery (Project Head Vögtle, Friederike-Nora )
• B06 - Adaptive remodeling of ribosome composition and function in response to metabolic changes and cellular stress (Project Head Koch, Hans-Georg )
• B07 - Non-equilibrium effects on the organization of protein machineries (Project Head Hugel, Thorsten )
• B08 - Interplay of the Hsp70 Ssb with ribosomes and cochaperones in the cytosol and at the ER membrane (Project Head Rospert, Sabine Karola )
• B09 - Ribonucleoprotein complex dynamics controlling LINE-1 retrotransposition and stress responses (Project Head Baumeister, Ralf )
• B10 - Modular assembly of the autophagy machinery in mitophagy and immunity (Project Heads Gámez-Díaz, Laura ;  Kraft, Claudine )
• B12 - Dynamics of the assembly, disassembly and molecular organization of the PII signaling machinery (Project Head Selim, Khaled )
• Z01 - Mass spectrometry platform for analysis of dynamic protein machineries (Project Heads Drepper, Friedel ;  Huesgen, Pitter ;  Schulte, Uwe ;  Warscheid, Bettina )
• Z02 - Central Coordination of the Collaborative Research Center (Project Head Meisinger, Chris )
• Z03 - Imaging dynamics of protein machineries and correlation with cellular topologies (Project Heads Hugel, Thorsten ;  Kraft, Claudine ;  Ott, Thomas )

Completed projects

• A08 - Biogenesis and activity-dependent dynamics of AMPA-receptor complexes (Project Head Fakler, Bernd )
• B01 - The KMT9 protein machinery is a novel chromatin writer (Project Head Schüle, Roland )
• B05 - Crosstalk between the mitochondrial respiratory chain and the cytosolic protein synthesis machinery (Project Head Warscheid, Bettina )
• B11 - Mechanism and dynamics of the nuclear localization of the human 26S proteasome (Project Head Haselbach, David )

• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Participating Institution: Max-Planck-Institut für Immunbiologie und Epigenetik
• Participating University: Ruprecht-Karls-Universität Heidelberg; Medizinische Fakultät Heidelberg
• Spokesperson: Professor Dr. Chris Meisinger