Project Details
SFB 642: GTP- and ATP-dependent Membrane Processes
Subject Area
Biology
Medicine
Medicine
Term
from 2004 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5486123
Membrane-dependent processes are central for the understanding of the transduction of external signals and matter into cells. In the postgenomic era proteins and their interactions in networks become more and more centered in the molecular-oriented biological research. The Collaborative Research Centre is focused on GTP- and ATP-dependent processes.
GTP-dependent membrane processes are essential for the transduction of external signals into cells, they are therefore central for the regulation of important biological processes, i. e., cell division. ATP-dependent mechanisms at membranes are significant for biochemical transport processes. The different processes are regulated by catalytic hydrolysis of the nucleotides, whose basic molecular and thermodynamical principles seem to be quite similar.
In the Collaborative Research Centre the common molecular reaction mechanisms of membrane processes are to be worked out. For this purpose 3D structures of the involved proteins, ligand binding, reaction kinetics and protein-protein interactions are studied. The following questions are addressed:
-- Which structural elements of a protein are important for its function?
-- Which proteins do interact with each other? How are the dynamics of these interactions defined?
-- Which changes of the protein structure lead to interaction? How are the kinetics of these interactions characterised?
-- At which time and location proteins are incorporated in the membrane? What role do lipid anchors play?
-- Which multi-enzyme complexes are formed?
-- What role does a protein play in a biological system (cell culture, animal model) and how is it influenced by modifications?
Since the membrane processes studied in the Collaborative Research Centre are affected by mutations of the involved proteins, diseases like cancer may evolve. Hence the answers to many of the questions will be highly relevant for medicinal purposes, exceeding the aims of basic research.
GTP-dependent membrane processes are essential for the transduction of external signals into cells, they are therefore central for the regulation of important biological processes, i. e., cell division. ATP-dependent mechanisms at membranes are significant for biochemical transport processes. The different processes are regulated by catalytic hydrolysis of the nucleotides, whose basic molecular and thermodynamical principles seem to be quite similar.
In the Collaborative Research Centre the common molecular reaction mechanisms of membrane processes are to be worked out. For this purpose 3D structures of the involved proteins, ligand binding, reaction kinetics and protein-protein interactions are studied. The following questions are addressed:
-- Which structural elements of a protein are important for its function?
-- Which proteins do interact with each other? How are the dynamics of these interactions defined?
-- Which changes of the protein structure lead to interaction? How are the kinetics of these interactions characterised?
-- At which time and location proteins are incorporated in the membrane? What role do lipid anchors play?
-- Which multi-enzyme complexes are formed?
-- What role does a protein play in a biological system (cell culture, animal model) and how is it influenced by modifications?
Since the membrane processes studied in the Collaborative Research Centre are affected by mutations of the involved proteins, diseases like cancer may evolve. Hence the answers to many of the questions will be highly relevant for medicinal purposes, exceeding the aims of basic research.
DFG Programme
Collaborative Research Centres
Completed projects
- A01 - Molecular mechanisms of small and heterotrimeric G proteins (Project Heads Gerwert, Klaus ; Kötting, Carsten )
- A02 - Synthesis, biophysical and biological evaluation of lipid modified Ras and Rab peptides. Identification of inhibitors of the Ras-PDEÔ interaction (Project Heads Waldmann, Herbert ; Wittinghofer, Alfred )
- A03 - Biophysical Characterization of Membrane-Associated Ras Signaling Processes (Project Heads Weise, Katrin ; Winter, Roland )
- A04 - Studies on the spatial and temporal distribution of Rab proteins in the cell (Project Heads Goody, Roger S. ; Wu, Yaowen )
- A05 - Mechanisms of apoptotic Ras pathways by multiprotein complex formation (Project Head Herrmann, Christian )
- A06 - Rheb enhances apoptosis - from in cell NMR spectroscopic structural and functional studies to in vivo effects of the adult mouse brainfunction (Project Heads Heumann, Rolf ; Stoll, Raphael )
- A07 - Structural Investigations of the nuclear pore in the context of membrane transport regulated by the small GTP-binding protein Ran (Project Head Vetter, Ingrid )
- A08 - Interaktion von Rho mit seinem downstream effector mDia und Modulierung des Aktinzytoskeletts (Project Head Wittinghofer, Alfred )
- A09 - Regulation des Axonwachstums und neuronaler Polarität durch Tenascin-C-Domänen, komplementäre Rezeptoren und kleine GTP bindende Proteine (Project Head Faissner, Andreas )
- A11 - Olfactory receptor associated protein complexes as regulatory element of chemosensory signal processing (Project Head Hatt, Hanns )
- A13 - ATP and GTP-dependent steps involved in peroxisomal biogenesis (Project Head Erdmann, Ralf )
- A15 - Studies of membrane-bound protein complexes and GPCR-mediated cellular processes by functional proteomics (Project Head Meyer, Helmut Erich )
- A16 - Spatial organization of Ras signaling (Project Head Bastiaens, Philippe )
- A17 - Regulation of the Lowe syndrome Proteins OCRL and INPP5B via Rab-Proteins (Project Head Erdmann, Kai Sven )
- A18 - Structural and biochemical studies on the specific regulation and ATPdependent modulation of receptor guanylyl cyclases (Project Head Steegborn, Clemens )
- A19 - Substrate-recognition and -degradation by the ATP-dependent, membrane-bound FtsH-protease in Escherichia coli (Project Head Narberhaus, Franz )
- A20 - The role of Arl6 and the BBSome in ciliary transport (Project Head Wittinghofer, Alfred )
- A21 - Mechanism of Ras deacylation at the membrane by acyl protein thioesterases and implications for Ras signal transduction (Project Head Vetter, Ingrid )
- A22 - Transport mechanism of the bacterial ABC-transporter MsbA (Project Head Hofmann, Eckhard )
- A23 - GTP-dependent processes involved in SRP-mediated protein transport in chloroplasts (Project Head Schünemann, Danja )
- A24 - Molecular regulatory mechanisms of synaptogenesis and synaptic maturation of central nervous system neurons and of the myelination of their axons by GTPases and the up-stream nucleotide exchange factor Vav3 (Project Head Faissner, Andreas )
- A25 - Regulation of the phosphatidylinositol 3-kinase dependent signal transduction (Project Head Platta, Harald )
- MGK - Integrated Research Training Group (Project Head Herrmann, Christian )
- V - Central tasks of the Collaborative Research Center (Project Head Gerwert, Klaus )
- Z - Quantitative mass spectrometry-based proteomics to analyze membrane proteins and membrane protein complexes (Project Heads Kuhlmann, Katja ; Marcus-Alic, Katrin ; Meyer, Helmut Erich ; Wolters, Dirk )
Applicant Institution
Ruhr-Universität Bochum
Participating University
Technische Universität Dortmund
Participating Institution
Max-Planck-Institut für molekulare Physiologie
Spokesperson
Professor Dr. Klaus Gerwert