SFB 610:  Variation in Protein Conformation: Cellbiological and Pathological Relevance

• Subject Area: Biology
• Term: from 2002 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5485142

The knowledge of protein conformation on a molecular level is of great relevance to our overall understanding of cellular mechanisms. Divergent conformations of proteins can be obtained by different folding, by different post translational modifications, but also by different interactions with biomolecular partners. In this project protein conformations shall be characterized by using aptamers (RNA molecules with specific binding properties), peptides or by means of molecular biological techniques, and analyzed by NMR, X-ray analysis or molecular modelling. The major targets either focus on proteins with conformation relevant for basic cellular activies like receptors, peptide ligases or adhesion molecules, or with protein conformations that play a role in diseases. These include heterochromatin proteins (multiple myeloma), the Tau-protein (Alzheimer disease) or poly(A)-binding proteins (oculopharyngeale muscledystrophy). Furthermore therapeutic strategies are investigated in which protein conformations shall be addressed. By using aptamers, peptides or virosomes e.g. association of matrixmetalloprotease and TIMP or viral protein cell interactions shall be inhibited. Any successful therapies of diseases based on pathological protein conformations rely on the molecular understanding of the principles. Only a big interdisciplinary research cooperation on the borderline of basic and applied biomedical research will be able to contribute and solve these problems.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - On the role of protein loops in the biosynthesis and in the ligand-receptor interaction of the neuropeptide Y system (Project Head Beck-Sickinger, Annette G. )
• A02 - Structural Dependence of the NH-Exchange Using Ubiquitin as an Example (Project Head Berger, Stefan )
• A03 - Proteinfoldase Parvulin 10: Funktionale Modifizierung durch native enzymatische Ligationskatalyse (Project Head Wehofsky, Nicole )
• A04 - Description of a novel proteolytic pathway in the cell as characterized by peptidyl prolyl cis/trans isomerase catalysis (Project Head Fischer, Gunter S. )
• A5 - Struktur- und Signalfunktion von armadillo-verwandten Proteinen - Analyse der Protein-Protein-Wechselwirkungen (Project Head Hatzfeld, Mechthild )
• A6 - Phosphorylierungsabhängige Interaktion zwischen dem Transkriptionsfaktor Stat3 und Coactivatoren bei der zytokingesteuerten Genregulation (Project Head Horn, Friedemann )
• A7 - Menschliche Heterochromatinproteine - Drosophila als Modellsystem zum Studium ausgewählter menschlicher Chromatinkrankheiten (Project Head Reuter, Gunter )
• A8 - Charakterisierung des krebsrelevanten Zuotinhomologs MPP11 (Project Head Rospert, Sabine Karola )
• A09 - Disease-associated, poly-alanine induced fibril formation and fibril structure of the nuclear poly(A) binding protein PABPN1 (Project Head Schwarz, Elisabeth )
• A10 - Conformational changes in intracellular domains of G protein-coupled receptors (Project Head Schöneberg, Torsten )
• A11 - G-protein-coupled receptors: prokaryotic expression, in vitro folding, purification and biophysical characterisation (Project Head Rudolph, Rainer )
• A12 - Spätzle splice variants in Drosophila signalling pathways (Project Head Stubbs, Milton T. )
• A13 - The mechanism of the prolyl isomerase SlyD (Project Head Balbach, Jochen )
• A14 - Determination of the Structure and Dynamics of Receptor-Bound Neuropeptide Y using Solid-State NMR Spectroscopy (Project Head Huster, Daniel )
• B1 - Modulation der Signaltransduktion und des Genexpressionsprofils durch Spleißvarianten des GM-CSF Rezeptors (Project Head Burdach, Stefan )
• B03 - Interaktionen zwischen Matrix Metallproteinasen, deren Fragmenten und ihren Protein-Inhibitoren (TIMPs) als therapeutische Targets (Project Head Gebhardt, Rolf )
• B4 - in vitro-Selektion Protin-Zustands-spezifischer Aptamere (Project Head Hahn, Ulrich )
• B05 - Design of artificial bifunctional proteins of therapeutic relevance, based on polyionic fusion peptides (Project Head Lilie, Hauke )
• B06 - Mechanismen der Neutralisation unbehüllter Viren, untersucht am Beispiel des Virus der infektiösen Bursitis (IBDV) (Project Head Müller, Hermann )
• B07 - Effects of different CD44 functional states on the biology of malignant melanoma: ADAM10-mediated shedding of CD44 (Project Head Simon, Jan-Christoph )
• B08 - Structure and allosteric conformations of eucaryotic 6-phosphofructokinases (Project Heads Schöneberg, Torsten ;  Sträter, Norbert )
• C01 - Function of the armadillo protein p0071 in cell polarity: coordination of cytoskeletal organization and vesicle transport and -fusion (Project Head Hatzfeld, Mechthild )
• C02 - Gene regulation by cytokines: Proteininteractions of the transcription factor Stat3 (Project Head Horn, Friedemann )
• C03 - Multimeric enzyme complexes and the control of chromatin states (Project Head Reuter, Gunter )
• C04 - The asymmetric dimethylation of arginine side chains in the nuclear poly(A)binding protein (PABPN1) (Project Head Wahle, Elmar )
• C05 - Functional domains and regulation of the oncofetal IMP proteins (Project Head Hüttelmaier, Stefan )
• MGK - Integrated Research Training Group (Project Heads Schöneberg, Torsten ;  Stubbs, Milton T. )
• N01 - Analysis of the structure and aggregation properties of natural and disease-related variants of the Alzheimer's Aß peptide (Project Head Fändrich, Marcus )
• T01 - Bio-electronik High Content Screening of drug candidates in cell culture and 3D (in vitro) tissue models for chronic neuropathies (Project Head Robitzki, Andrea A. )
• Z03 - Molecular Modelling (Project Heads Günther, Robert ;  Hofmann, Hans-Jörg )
• Z04 - Zentrale Aufgaben des Sonderforschungsbereichs (Project Head Beck-Sickinger, Annette G. )
• Z05 - Functional analysis of protein modifications using cell and tissue based biosensors (Project Head Robitzki, Andrea A. )

• Applicant Institution: Universität Leipzig
• Participating University: Martin-Luther-Universität Halle-Wittenberg
• Participating Institution: Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. (MPG)
• Spokesperson: Professorin Dr. Annette G. Beck-Sickinger