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Biomacromolecular structures, dynamics and interactions by NMR and new developments in NMR technology.

Research Project
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01.10.2010
 - 30.09.2013

Summary Biological function is almost uniquely exerted via interactions of biomacromolecules. Such interactions are still poorly understood and often involve large conformational changes, in extreme cases even from completely unfolded to folded structures. High resolution NMR has emerged as one of the most versatile tools for a precise description of biomolecules and their interactions, not only in terms of static structures, but also by kinetic, energetic, and thermodynamic parameters at the atomic level. It is the goal of this proposal to use and to develop the unique strengths of NMR to arrive at a more quantitative understanding of biomolecules and their interactions. The proposal is divided into two subprojects: Subproject A is directed towards the determination of structure, dynamics, and interactions in a number of protein systems where we have detailed biological information from in-house or external collaborations, but no or insufficient structural and dynamical data are available, and where solution NMR methods are expected to yield unique new information. Specifically, this subproject addresses protein-protein and protein-ligand interactions in cadherin-mediated cellular adhesion, antiobiotic resistance in Streptomyces, proteins of the Yersinia injectisome, the Bartonella type IV secretion system, and proteins involved in transcriptional elongation as well as nematocyst wall formation. In addition, we want to characterize the interactions of lipopolysaccharides (endotoxins) by novel NMR methods. Subproject B is directed towards the development of novel NMR methods with a specific focus on the precise description of folding in model systems and of hydrogen bonds. In particular, it seems now possible to obtain a complete geometric description of the folding of peptides and small proteins in terms of angular distributions and order parameters from residual dipolar couplings. This could finally lead to a complete thermodynamic description of folding transitions in peptides and small proteins. We also want to continue our research on the spectroscopy of biomolecular hydrogen bonds with an emphasis on the influence of biomolecular dynamics on hydrogen bond parameters and a comparison between the thermodynamic behavior of protein and nucleic acid hydrogen bonds. The goal is to determine to what extent H-bonds contribute to the overall thermodynamic properties of biomolecules. Finally, we also want to start an exploratory project in solid state NMR of biomolecules with the goal to describe the influence of crystalline and non-crystalline environment on the line width of biomolecules in solid state NMR spectra.

Collaborations & Cooperations

2019 - Participation or Organization of Collaborations within own University
Schirmer, Tilman, Prof., Universität Basel, Research cooperation
2014 - Participation or Organization of Collaborations within own University
Jenal, Urs, Prof, Universität Basel, Research cooperation
2013 - Participation or Organization of Collaborations within own University
Stahlberg Henning, Prof., Universität Basel, Research cooperation
2013 - Participation or Organization of Collaborations on a national level
Jahnke Wolfgang, Dr., Novartis Basel, Research cooperation
2013 - Participation or Organization of Collaborations on a national level
Schertler Gebhard, Prof., Paul Scherrer Institut, Research cooperation
2013 - Participation or Organization of Collaborations on an international level
Baldus Marc, Prof., University of Utrecht, Research cooperation
2013 - Participation or Organization of Collaborations on an international level
Blackledge Martin, Dr., IBS Grenoble, Research cooperation
2013 - Participation or Organization of Collaborations on an international level
Emsley Lyndon, Prof., ENS Lyon, Research cooperation
2013 - Participation or Organization of Collaborations on an international level
Zähringer Ulrich, Prof., Forschungszentrum Borstel, Research cooperation

Publications

Bigalke, Janna M. et al. (2011) ‘Structure and Dynamics of a Stabilized Coiled-Coil Domain in the P-TEFb Regulator Hexim1’, Journal of Molecular Biology, 414(5), pp. 639–53. Available at: https://doi.org/10.1016/j.jmb.2011.10.022.

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Dames, Sonja A. et al. (2011) ‘Structure, dynamics, lipid binding, and physiological relevance of the putative GTPase-binding domain of Dictyostelium formin C’, Journal of Biological Chemistry, 286(42), pp. 36907–20. Available at: https://doi.org/10.1074/jbc.m111.225052.

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Habazettl, Judith et al. (2011) ‘Solution structure of the PilZ domain protein PA4608 complex with cyclic di-GMP identifies charge clustering as molecular readout’, Journal of biological chemistry, 286(16), pp. 14304–14. Available at: https://doi.org/10.1074/jbc.m110.209007.

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Lewandowski, Józef R. et al. (2011) ‘Site-specific measurement of slow motions in proteins’, Journal of the American Chemical Society, 133(42), pp. 16762–5. Available at: https://doi.org/10.1021/ja206815h.

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Grzesiek, Stephan and Becker, Edwin D. (2011) ‘Hydrogen bonding’, in Harris, Robin K.; Wasylishen, Roderick E. (ed.) Encyclopedia of NMR. Chichester: John Wiley (Encyclopedia of NMR), pp. 1929–1935. Available at: https://doi.org/10.1002/9780470034590.emrstm0216.pub2.

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Vuister, Geerten W. et al. (2011) ‘Measurement of structural restraints in ‘A guide to protein NMR spectroscopy’’, in Lian, Lu-Yun; Roberts, Gordon (ed.) Protein NMR spectroscopy : principal techniques and applications. Chichester: John Wiley & Sons (Protein NMR spectroscopy : principal techniques and applications), p. S. 351.

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Members (1)

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Stephan Grzesiek

Principal Investigator