Book of Abstracts: Albany 2007
June 19-23 2007
DNA and RNA Branching: NMR structural studies
Branched nucleic acids play not only crucial biological roles they can also function as designable building blocks in nano-technology. An overview of our structure work on branched nucleic acids will be given, paying attention to their structure-function relationships. NMR structure determination has for a long time relied on NOEs, which provide (short) distance measures. Unfortunately the extended and domain nature of many RNAs and DNAs has prohibited their structure determination by means of NMR. Thanks to the development of methods to measure residual dipolar couplings, which provide global structure information, reliable structure determination of branched nucleic acids has become possible. Furthermore, development of new labeling technologies in our lab, e.g. in-vitro specific labeling of RNA and DNA with 13C, 15N, and 2H combined with segmental labeling methods, can largely reduce resonance overlap in larger nucleic acid molecules. These methodologies open the route for structure determination of RNAs and DNAs of a size up to 100 to 150 nucleotides and thus for studying really functional units with branched DNA or RNAs embedded in them. These methodologies will be touched upon together with the structures discussed. We will present the high-resolution NMR structure of a DNA Holliday junction in complex with its multivalent ion that induces the stacked fold, structures of DNA three-way junctions and show preliminary results on three-way junction folding in triple repeat sequences found in the DNA of patients with Huntington?s disease. Finally, the global structure of the RNA three-way junction present in the aptamer of a riboswitch will be presented and its function discussed.
Biophysical Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, The Netherlands. Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.