Protein NMR
Prof M P Williamson |
Career History2001-present: Professor, University of Sheffield |
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| We have been developing new tools to characterise volume fluctuations in proteins, which occur on timescales between ns and ms. In particular, we have shown that changes in the NMR spectrum resulting from hydrostatic pressures of up to 2 kbar can be used to show how proteins move, and also how they start to denature under pressure. The mobilities are greatest at the active site, and usually involve buried water molecules, which are very important for increasing local flexibility (Figure 1). |
| We have demonstrated that exposed salt bridges are not energetically favourable in solution, even though they are often observed in crystals |
| In collaboration with Prof Hunter in MBB, we have determined structures for two trans-membrane proteins involved in bacterial light-harvesting. The structures are very similar in organic solvents and in micelles. These structures have been used to model the intact photosynthetic complex |
| We have studied how proteins recognize polysaccharides such as starch, cellulose and xylan. The activities of enzymes that degrade these plant polymers tend to be organized into ‘cellulosomes’ which are large assemblies of many different enzymes. We have determined the structure of the key assembly component of the anaerobic cellulosome and showed that it probably relies on protein / carbohydrate recognition to assemble |
| We have a longstanding interest in polyphenols such as those from tea, and in how they interact with the body. As part of this study, we have shown that the main component of green tea, epigallocatechin gallate, has the potential to slow down HIV infection. |
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 Figure 1– Slow fluctuations in the ribonuclease barnase. In blue are residues that become significantly less mobile on binding to ligands (shown in red). These residues define a ‘hinge-bending’ region important for ligand binding. The spheres show the location of buried water molecules. |
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find me on Google Scholar |
Selected PublicationsBook published July 17 2011: Chapter 1 Protein structure and evolution; Chapter 2 Protein domains; Chapter 3 Oligomers; Chapter 4 Protein interactions in vivo; Chapter 5 How enzymes work; Chapter 6 Protein flexibility and dynamics; Chapter 7 How proteins make things move; Chapter 8 How proteins transmit signals; Chapter 9 Protein complexes: molecular machines; Chapter 10 Multi-enzyme complexes; Chapter 11 Techniques for studying proteins.
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| Two different packing arrangements for antiparallel polyalanine, T. Asakura, M. Okonogi, K. Horiguchi, A. Aoki, H. Saitô, D. P. Knight and M. P. Williamson, Angewandte Chemie, 2012, 51, 1212-1215. |
| Ab initio calculations of deuterium isotope effects on chemical shifts of salt-bridged lysines, S. Ullah, T. Ishimoto, M. P. Williamson and P. E. Hansen, J. Phys. Chem. B., 2011, 115, 3208-3215. |
| Experimental evidence that the membrane-spanning helix of PufX adopts a bent conformation that facilitates dimerisation of the Rhodobacter sphaeroides RC-LH1 complex through N-terminal interactions, E. Ratcliffe, R. B. Tunnicliffe, I. W. Ng, P. Adams, P. Qian, K. Holden-Dye, M. R. Jones, M. P. Williamson and C. N. Hunter, BBA Energetics, 2011, 1807, 95-107. |
| Structural origins of pH-dependent chemical shifts in protein G, J. H. Tomlinson, V. L. Green, P. J. Baker and M. P. Williamson, Proteins: Struct., Funct. Bioinf., 2010, 78, 3000-3016. |
| Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and regulates NF-κB signalling , J. Long, T. P. Garner, M. J. Pandya, C. J. Craven, P. Chen, B. Shaw, M. P. Williamson, R. Layfield and M. S. Searle, J. Mol. Biol., 2010, 396, 178-194. |
| A polycystin-2 dimerization domain essential for the function of heteromeric polycystin complexes, A. Giamarchi, S. Feng, L. Rodat-Despoix, Y. Xu, E. Bubenshchikova, L. J. Newby, J. Hao, C. Gaudioso, M. Crest, A. N. Lupas, E. Honoré, M. P. Williamson , T. Obara, A. C. M. Ong and P. Delmas, EMBO J 2010 29:1176-1191. |
| Dimerization of protein G B1 domain at low pH: A conformational switch caused by loss of a single hydrogen bond. Tomlinson JH, Craven CJ, Williamson MP, Pandya MJ. Proteins. 2010 78:1652-1661. |
| Structure of the Complex of [Ru(tpm)(dppz)py](2+) with a B-DNA Oligonucleotide-A Single-Substituent Binding Switch for a Metallo-Intercalator. Waywell P, Gonzalez V, Gill MR, Adams H, Meijer AJ, Williamson MP, Thomas JA. Chemistry. 2010 Jan 27;16(8):2407-2417. |
| Pressure-dependent structure changes in barnase on ligand binding reveal intermediate rate fluctuations. Wilton DJ, Kitahara R, Akasaka K, Pandya MJ, Williamson MP. Biophys J. 2009 Sep 2;97(5):1482-90. |
| Characterization of salt bridges to lysines in the protein G B1 domain. Tomlinson JH, Ullah S, Hansen PE, Williamson MP. J Am Chem Soc. 2009 Apr 8;131(13):4674-84. |
| Automated protein structure calculation from NMR data. Williamson MP, Craven CJ. J Biomol NMR. 2009 Mar;43(3):131-43. |
| Pressure induced changes in the solution structure of the GB1 domain of protein G, D. J. Wilton, R. B. Tunnicliffe, Y. O. Kamatari, K. Akasaka and M. P. Williamson, Proteins 2008, 71,1432-1440. |
| Characterisation of a double dockerin from the cellulosome of the anaerobic fungus Piromyces equi, T. Nagy, R. B. Tunnicliffe, L. D. Higgins, C. Walters, H. J. Gilbert and M. P. Williamson, J. Mol. Biol., 2007, 373 612-622. |
| Epigallocatechin gallate, the main polyphenol in green tea, binds to the T cell receptor CD4: Potential for HIV-1 therapy, M. P. Williamson, T. G. McCormick, C. L. Nance and W. T. Shearer, J. Allergy Clin. Immunol. 2006, 118 1369-1374. |
| An experimental investigation of conformational fluctuations in proteins G and L, R. B. Tunnicliffe, J. L. Waby, R. J. Williams and M. P. Williamson, Structure 2005 13 1677-1684. |
My laboratory uses NMR (and other methods where appropriate) to determine the structure and dynamics of proteins in solution and to study their interactions with ligands. In addition we are developing new methods for characterising structures. Further details are in my web page, linked on the right. Recent work includes: