Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

Tel: +44 (0)1865 613200
Fax: +44 (0)1865 613201
Image showing the global movement of lipids in a model planar membrane
Matthieu Chavent, Sansom lab
Anaphase bridges in fission yeast cells
Whitby lab
Lactose permease represented using bending cylinders in Bendix software
Caroline Dahl, Sansom lab
Epithelial cells in C. elegans showing a seam cell that failed to undergo cytokinesis
Serena Ding, Woollard lab
Collage of Drosophila third instar larva optic lobe
Lu Yang, Davis lab
First year Biochemistry students at a practical class
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Anthony Watts
Resolving structural details of membrane peptides and proteins at high resolution

Co-workers: Juan Bada Juarez, Juan Bolivar Gonzalez, Claudia Cassidy, Patricia Dijkman, Peter Fisher, Stephanie Gover, Alice Hart, Rosana Inácio dos Reis, Peter Judge, Steven Lavington, Juan Munoz-Garcia, Marc-Philipp Pfeil, Daniel Yin, Soumia Zeghida.

Resolving structural details of membrane receptors is still a major challenge, not least because of the difficulties of expression, crystallization and their size. Since membrane protein secondary structure can be modelled for many cases, we have been devising solid state NMR methods for determining high resolution (sub-Å) details of information-rich sites within membrane receptors (Watts, A., 2005. Nature Reviews Drug Discovery, 4, 555-568). In particular, we have resolved new information about ligand (drug, neurotransmitter or solute) binding sites, and related all this information to functional descriptions.

Our recent focus has been on the neurotensin receptor (NTS1) which we have expressed in E. coli in structural biology amounts (Attrill et al, 2009, J. Express & Purif, 64, 32-38) in a functionally competent form for structural studies, some of which involve single molecule approaches for bionanotechnological and drug design applications.

NTS1 is now available highly purified monodispersed in detergent and in a ligand-binding form. One approach to monitoring ligand binding has been to develop a novel surface plasmon resonance method for tagging the natural ligand, neurotensin (13-mer peptide), to the chip and monitoring protein binding (Harding et al., 2006, Euro. Biophys. J., 35, 709-712). Fluorescently tagged NTS1 has also been used in fluorescence resonance energy transfer methods to resolve long range information of protein-protein signalling (Harding, et al., 2009, Biophsy. J., 96, 964-973).

Publications - 2015 

 Publications - 2014

Publications - 2013

Publications - 2012

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A Fascination with Vision - a video lecture for non-specialists

Research Images

Figure 1: Substituted imidazo-pyridines are inhibitors of the gastric H+/K+-ATPase. By specific labelling of members of this drug family with NMR visible isotopes, we have been able to define the full conformation of the bound ligand, and suggest mechanism for inhibition from homology modelling with a related protein. (Kim, Watts & Watts, 2005, J. Med. Chem. 48, 7145-7152 and Watts, Watts & Middleton, 2001, J. Biol. Chem., 276, 43197-43204).

Figure 2: The cation-π interaction of acetyl choline, a major brain neurotransmitter, and the ligand gated, nicotinic acetyl choline receptor has been resolved using solid state NMR, giving an insight into the binding mechanism and the residues surrounding the site. (Watts, 2005, Nature Reviews Drug Discovery, 4, 555-568; Williamson et al., 2007, PNAS, 104, 18031-18036)

Figure 3: The way in which retinal is restrained within its binding site in membrane-embedded mammalian rhodopsin, and the structural details of the site, have been resolved for the early activation states of this light-activated GPCR, using high resolution solid state NMR to measure atomic distances within the retinal to high accuracy (+/- 0.2Å). (Spooner, et al., 2004, J. Mol. Biol., 343, 719-730)
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