Nuclear magnetic resonance (NMR) spectroscopy is the most powerful physical method available for the study of molecular structure in the solution state, probing interactions between individual atomic nuclei to reveal their spatial relationships and dynamic properties.
Over recent years, the technique has become steadily more sensitive and widely applicable. At LMB, we use NMR spectrometers with field-strengths ranging from 400MHz to 800MHz, and by combining state-of-the-art, multi-dimensional NMR experiments with sample preparation strategies that employ carefully devised labelling patterns of stable isotopes (e.g. 13C, 15N, 2H), we are able to study detailed three-dimensional solution structures and dynamics in many important biological systems.
A particular strength of NMR is its ability to reveal the structural details of specific interactions between biological macromolecules, especially proteins, and their targets in solution; this is often of crucial importance in understanding the underlying basis of function. We have been using NMR to determine structures and interactions in a variety of highly challenging systems, including particularly proteins and complexes involved in the areas of DNA repair, chromatin targeting, nuclear trafficking, mRNA splicing and vesicle trafficking.
Selected Papers
- Eustermann, S.E., Wu, W.F., Langelier, M.F., Yang, J.C., Easton, L.E., Riccio, A.A., Pascal, J.M. and Neuhaus, D. (2015)
Structural basis of detection and signalling of DNA single-strand breaks by human PARP-1
Molecular Cell 60: 742-754 - van Roon, A.-M. M., Yang, J. C., Mathieu, D., Bermel, W., Nagai, K. and Neuhaus, D. (2015)
113Cd NMR Experiments Reveal an Unusual Metal Cluster in the Solution Structure of the Yeast Splicing Protein Bud31p
Angewandte Chemie International Edition 54: 4861-4864. - Eustermann, S., Videler, H., Yang, J.-C., Cole, P. T., Gruszka, D., Veprintsev, D. and Neuhaus, D. (2011)
The DNA-binding domain of human PARP-1 interacts with DNA single-strand breaks as a monomer through its second zinc finger.
Journal of Molecular Biology 407: 149-170. - Eustermann, S., Yang, J.-C., Law, M. J., Amos, R., Chapman, L. M., Jelinska, C., Garrick, D., Clynes, D., Gibbons, R. J., Rhodes, D., Higgs, D. R. and Neuhaus, D. (2011)
Combinatorial readout of histone H3 modifications specifies localisation of ATRX to heterochromatin.
Nature Structural and Molecular Biology 18: 777-782. - Eustermann, S., Brockmann, C., Mehrotra, P. V., Yang, J. C., Loakes, D., West, S. C., Ahel, I. and Neuhaus, D. (2010)
Solution structures of the two PBZ domains from human APLF and their interaction with poly(ADP-ribose).
Nat Struct Mol Biol. 17: 241-243. - van Roon, A.M.M., Loening, N.M., Obayashi, E., Yang, J.-C., Newman, A.J.,Hernandez, H., Nagai K. and Neuhaus, D. (2008)
Solution structure of the U2snRNP protein RDS3p reveals a knotted zinc finger motif.
Proc Natl Acad Sci U.S.A. 105: 9621-9626.
Group Members
- Harriet Crawley-Snowdon
- Laura Easton
- William Hawthorne
- Leo Kiss
- Tom Ogden
- Ji-Chun Yang