Publication Details (including relevant citation information):
Pederson, K.; Echodu, D.; Emani, P.; Olsen, G.; Bardaro, M. F. J.; Shajani, Z.; Meints, G.; Miller, P.; Varani, G.; Drobny, G. P. In Encyclopedia of Magnetic Resonance 2010.
The last few years have seen a remarkable increase in interest in the role of protein motion in catalysis, the energetics of protein folding and molecular recognition. While motion and conformational adaptation is also very important for nucleic acids (many RNAs and DNAs function by undergoing large conformational changes in response to binding of a protein or small molecule), it is still not clear how motion contributes to the function of nucleic acids. There is a clear need to study motions and conformational transitions of nucleic acids by applying biophysical techniques that extend the description of DNA and RNA beyond the familiar static structures. It is well known that different dynamic spectroscopies display variable sensitivity to different rates of motion; therefore, to rely upon any single type of spectroscopic measurement runs the risk of obtaining either an incomplete or incorrect description of internal molecular motions. Here we use solution and solid-state NMR to study the dynamics for two paradigmatic nucleic acid systems whose biological function depends on their ability to change structure: the flipping out of a deoxycytidine by the HhaI methyltransferase and TAR RNA which must undergo a structural rearrangement of its bulged loop to bind to the tat protein. In both cases, structures in the absence and presence of ligand are well described. Yet, little experimental data exists to define over the dynamic pathways linking these states, and how they depend on sequence. In both cases we use solid-state 2H NMR line shapes to probe for the presence of internal motions in the ms-ns timescales and relaxation to investigate dynamics at ns and shorter. We show that solid-state NMR can quantify motions at time scales not easily probed by solution NMR relaxation techniques and we show that solution and solid-state NMR views of the internal and overall rotations of these molecules can produce a unified view of the dynamics of these biomolecular systems.