Structure Determination

The knowledge of nucleic acid structures grew rapidly over the past decades and generated almost 10’000 3D-structures of nucleic acids or nucleic acid-protein complexes in the PDB database. 95% of these structures were solved either by x-ray crystallography or Nuclear Magnetic Resonance (NMR) spectroscopy. Both techniques were applied in the 3D-structure determination of biomolecules from the very start and are the most predominant techniques until today.

X-ray crystallography provides precise molecular structures and allows to gain insights into hydration pattern, ion binding and nucleic acid-ligand interactions. Together with beamline scientists of the Swiss Light Source (SLS) at the Paul Scherrer Institute and its excellent infrastructure, we investigate the structural and functional role of metal ions in RNA. By means of X-ray crystallography we are able to solve important structural states of RNA in order to understand the function of metal ions in RNA folding.

NMR spectroscopy is not only a powerful technique to obtain precise 3D-structures of nucleic acids but also to get a good overall understanding of their dynamic behavior as well as to draw a detailed picture of their interactions with metal ions.

We use a combination of isotope labeling strategies and various homo- and heteronuclear 2D and 3D NMR experiments to investigate how metal ions bind to nucleic acids and by that control the folding and the structure of these biomolecules.  For this purpose, we also apply NMR active metal ions (e.g. ¹¹³Cd, ¹⁰⁹Ag, ¹⁹⁹Hg) that can be directly detected.

Michelle F. Schaffer, Guanya Peng, Bernhard Spingler, Joachim Schnabl, Meitian Wang, Vincent Olieric, Roland K. O. Sigel*, Int. J. Mol. Sci., 2016, 17, 988.
doi:10.3390/ijms17070988

Maria Pechlaner, Daniela Donghi, Veronika Zelenay, Roland K. O. Sigel*, Angew. Chem. Int. Ed., 2015, 54, 9687-9690. Angew. Chem., 2015, 127, 9823-9826.
doi:10.1002/anie.201504014
doi:10.1002/ange.201504014

Daniela Kruschel, Miriam Skilandat, Roland K. O. Sigel*, RNA, 2014, 20, 295-307.
doi:10.1261/rna.041137.113

Miriam Skilandat, Roland K. O. Sigel*, J. Biol. Chem., 2014, 289, 20650 - 20663.
doi:10.1074/jbc.M113.542381

Daniela Donghi, Maria Pechlaner, Cinzia Finazzo, Bernd Knobloch, Roland K. O. Sigel*, Nucleic Acids Res. 2013, 41, 2489-2504.
doi:10.1093/nar/gks1179

Siriporn Phongtongpasuk, Susann Paulus, Joachim Schnabl, Roland K. O. Sigel*, Bernhard Spingler*, Michael J. Hannon*, Eva Freisinger*, Angew. Chem. Int. Ed., 2013, 52, 11513-11516.
doi:10.1002/anie.201305079

Silke Johannsen, Nicole Megger, Dominik Böhme, Roland K. O. Sigel*, Jens Müller*, Nature Chem., 2010, 2, 229-234.
doi:10.1038/NCHEM.512

Michèle C. Erat, Oliver Zerbe, Thomas Fox, Roland K. O. Sigel*, ChemBioChem, 2007, 8, 306-314.
doi:10.1002/cbic.200600459