Our group is focusing on structure-function analysis of proteins and protein-protein complexes in solution using NMR spectroscopy. We are especially interested in the type III protein secretion system. When bacteria attack another organism, one of the first steps is the injection of 'virulence effector proteins' into its cells. For many bacterial pathogens a key component in this process is a type III protein secretion system. It comprises more than 20 proteins and associated chaperones, and is closely related to the flagellar assembly apparatus. The current model of chaperone-assisted type III secretion indicates an important role for unfolded or partially folded effector proteins. This makes NMR spectroscopy the method of choice to clarify the mechanism of chaperone-assisted type III secretion.

In addition, we are extending the range of biomolecular questions that can be addressed by NMR. This includes design of novel NMR experiments, analysis tools and bioinformatics approaches. In light of the worldwide structural genomics effort, special emphasis is put on acceleration of biomolecular NMR studies of proteins and protein-protein complexes. A major component of these studies are residual dipolar couplings. Residual dipolar couplings promise to increase the accuracy of NMR structures, to make bigger proteins accessible to NMR and to allow the extraction of novel structural and dynamical information such as relative orientation of domains and medium-to-large scale inter-domain dynamics.

References

Rumpel, R., Razeto, A., Pillar, C.M., Vijayan, V., Giller, K., Gilmore, M.S., Becker, S. and Zweckstetter, M. , "Structure and DNA-binding properties of the cytolysin regulator CylR2 from Enterococcus faecalis ", EMBO J., 23, 3632-3642 (2004).

Zweckstetter, M. and Bax, A., "Prediction of sterically induced alignment in a dilute liquid crystalline phase: Aid to protein structure determination by NMR", Journal of the American Chemical Society, 122, 3791-3792 (2000).

Jung, Y.S., Sharma, M. and Zweckstetter, M., "Simultaneous assignment and structure determination of protein backbones by using NMR dipolar couplings", Angew. Chem.-Int. Edit., 26, 3479-3481 (2004).