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, vesicle trafficking, chromatin targeting and intracellular immunity.
Selected Papers
- Suskiewicz, M. J., Zobel, F., Ogden, T. E. H., Fontana, P., Ariza, A., Yang, J.-C., Zhu, K., Bracken, L., Hawthorne, W. J., Ahel, D., Neuhaus, D., Ahel, I. (2020)
HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation
Nature 579: 598-602. - Kiss, L., Zeng, J., Dickson, C. F., Mallery, D. L., Yang, J.-C., McLaughlin, S. H., Boland, A., Neuhaus, D., James, L. C. (2019)
A tri-ionic anchor mechanism drives Ube2N-specific recruitment and K63-chain ubiquitination in TRIM ligases
Nature Communications 10: 4502. - Wrobel, A. G., Kadlecova, Z., Kamenicky, J., Yang, J.-C., Herrmann, T., Kelly, B. T., Mccoy, A. J., Evans, P. R., Martin, S., Muller, S., Sroubek, F., Neuhaus, D., Honing, S., Owen, D. J. (2019)
Temporal Ordering in Endocytic Clathrin-Coated Vesicle Formation via AP2 Phosphorylation
Developmental Cell 50: 494-508. - Hedgethorne, K., Eustermann, S., Yang, J.-C., Ogden, T. E. H., Neuhaus, D., Bloomfield, G. (2017)
Homeodomain-like DNA-binding proteins control the haploid-to-diploid transition in Dictyostelium
Science Advances 3: e1602937. - 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.
Group Members
- Laura Easton
- William Hawthorne
- Leo Kiss
- Tom Ogden
- Ji-Chun Yang