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Chemical & Structural Biology

Development of New NMR Techniques for Monitoring of Protein Folding with Atomic Resolution

We have developed two independent methods to study structural transitions and reactions by time-resolved NMR spectroscopy with millisecond dead-time. Therefore, on one hand, we use a rapid mixing system inside the active volume in the probe, which we developed in cooperation with BRUKER. In addition, we have developed a method to laser-trigger cofactor dependent reactions inside the NMR tube which we established. These studies are supported by a wide variety of other spectroscopic techniques including stopped-flow fluorescence, CD, FTIR and EPR to gain further insight in structural characteristics during the folding process. At the moment we are focusing on the structural characterization of transient intermediates in protein folding. We are studying the kinetics of the natural structural changes of a-lactalbumine and calmoduline upon ion addition in cellular conditions, the binding kinetics of calmoduline to the calcium-pump receptor peptides and the refolding from denaturating reagents of calmodulin, a-lactalbumine, lysozyme and ubiquitin.

NMR studies of the structure and dynamics of the ribosomal protein L11 from Thermotoga maritima.

L11 is highly conserved ribosomal protein and its interaction with the ribosomal RNA segment from 23S subunit is considered to undergo an „induced fit“-conformational adjustment of both the protein and the RNA with respect to their conformations in the unbound state (Leulliot and Varani, 2001; Draper et al., 1996). Furthermore, the conformational dynamics of L11 are thought to play an important role in the binding process.

Comparison of the NMR Spectroscopy Solution Structure of Pyranosyl-RNA and Its Nucleo-delta-peptide Analogue

For all biological systems, nature has chosen ribo- and deoxyribonucleic acids as its genetic building block. In order to understand this selectivity, the structures of the potential alternatives to the natural nucleic acids have to be investigated. We have determined the solution structures of pRNA and Nucleo-d-peptides by NMR spectroscopy. The structures pose important questions about the origin of helicity, stacking and inclination of these oligomers.