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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Christina Redfield
NMR studies of protein structure, function, folding and dynamics

Co-workers: Antonio Biasutto, Andrew Johnston, Despoina Mavridou, Ian Robertson, Shevket Shevket, NIcola Steinke, Lorena Varela-Alvarez

Our research is highly collaborative and involves the application of solution-state NMR methods to address a range of biological problems. The NMR facility, housed in the Rex Richards Building, is equipped with spectrometers operating at 1H frequencies of 500, 600, 750 and 950 MHz. Current projects include:

(1) In collaboration with Professor Stuart Ferguson, we are using NMR to study the active-site properties and interactions of DsbD, a transmembrane oxidoreductase involved in the disulfide bond (Dsb) and cytochrome c maturation (Ccm) pathways in the bacterial periplasm (Figure 1). NMR is also being used to gain insights into the manner in which CcmE interacts with heme. 

(2) In collaboration with Professor Penny Handford, we are using NMR to characterise the structure, dynamics, interactions and Ca2+-binding properties of EGF domains in proteins including fibrillin-1, LTBP and Notch-1 and to understand how single amino acid substitutions can perturb these proteins and result in disease.

(3) In collaboration with Professor Judy Armitage, we are using NMR to study the structure, dynamics and interactions of proteins involved in bacterial chemotaxis. Rhodobacter sphaeroides has multiple chemosensory pathways formed by homologues of the E. coli

chemosensory proteins. It has six homologues of the response regulator CheY with different effects on chemotaxis. NMR is being used to define the structure and function of two of these, CheY3 and CheY6.

(4) Lysozyme from bacteriophage l is observed in open and closed conformations in X-ray structures. In collaboration with Dr Andre Matagne (Liege) and Dr Lorna Smith (Chemistry) we have used 15N relaxation methods (Figure 2) and residual dipolar couplings to show that these conformers interconvert rapidly in solution.

(5) The folding of a protein to its functional native state from the information encoded in its amino acid sequence is a key feature of the conversion of genetic information into biological activity. For some proteins partially structured species, known as molten globules, have been observed to form early in folding prior to the formation of the native state. We use NMR to define, at the level of individual residues, the determinants of the structure and stability of the molten globule states of proteins including α-lactalbumin.    


  1. D.A.I. Mavridou, E. Saridakis, P. Kritsiligkou, A.D. Goddard, J.M. Stevens, S.J. Ferguson and C. Redfield, Oxidation-state-dependent protein-protein interactions in disulfide cascades, J. Biol. Chem. 286, 24943-24956 (2011) 
  2. L.J. Smith, A. Bowen, A. DiPaolo, A. Matagne and C. Redfield, The Dynamics of Lysozyme from Bacteriophage Lambda in Solution probed by NMR and MD simulations, ChemBioChem 14, 1780-8 (2013)
  3. D.A. Yadin, I.B. Robertson, J. McNaught-Davis, P. Evans, D. Stoddart, P.A. Handford, S.A. Jensen and C. Redfield, Structure of the fibrillin-1 N-terminal domains suggests heparan sulphate regulates the early stages of microfibril assembly, Structure 21, 1743-56 (2013)
  4. I.B. Robertson, P.A. Handford and C. Redfield, Analysis of the LTBP1 C-terminus reveals a highly dynamic domain organization, PLoS ONE  9(1):e87125. doi: 10.1371/ journal.pone.0087125 (2014)
  5. D.A.I. Mavridou, E. Saridakis, P. Kritsiligkou, E.C. Mozley, S.J. Ferguson and C. Redfield, An extended active-site motif controls the reactivity of the thioredoxin fold. J. Biol. Chem. 289, 8681-96 (2014)
  6. K. Haslinger, C. Redfield and M.J. Cryle, Structure of the terminal PCP domain of the non-ribosomal peptide synthetase in teicoplanin biosynthesis. Proteins DOI:10.1002/prot.24758 (2015)
  7. G. Papadakos, A. Sharma, L.E. Lancaster, R. Bowen, R. Kaminska, A.P. Leech, D. Walker, C. Redfield and C. Kleanthous, The consequences of inducing intrinsic disorder on a high affinity protein-protein interaction. J. Am. Chem. Soc. 137(16),5252-5255 (2015)
  8. K. Tozawa, S.J. Ferguson, C. Redfield and L.J. Smith, Comparison of the backbone dynamics of wild-type Hydrogenobacter thermophiles cytochrome c552 and its b-type variant. J. Biomol. NMR, 62, 221-231 (2015).
  9. P.C. Weisshuhn, D. Sheppard, P. Taylor, P. Whiteman, S.M. Lea, P.A. Handford and C. Redfield, Non-linear and flexible regions of the human Notch-1 extracellular domain revealed by high-resolution structural studies, Structure in press.
More Publications...

Research Images

Figure 1: Schematic representation of the reaction cycle involving the N- and C-terminal domains of DsbD (nDsbD and cDsbD). (I) C461, the attacking cysteine residue in cDsbD, has an elevated pKa value of 10.5 when cDsbDred is distant from nDsbD. This makes C461 a poor nucleophile, as essentially only the thiol species will be present, and protects cDsbDred from non-specific oxidation by other periplasmic proteins. (II) The relatively high affinity of nDsbDox for cDsbDred (Kd 86 uM) ensures formation of the nDsbDox·cDsbDred complex at the high effective concentration found in intact DsbD. In close proximity to nDsbD, the pKa value of C461 in cDsbDred is lowered by as much a 2 pH units. This increases the concentration of the reactive thiolate species (S-) making C461 a better nucleophile. C461 will attack the disulfide bond of nDsbDox allowing electron transfer to proceed via a mixed-disulfide covalent intermediate. (III) The lower affinity of the two protein partners in the nDsbDred·cDsbDox complex (Kd > 2 mM) ensures dissociation following electron transfer. (IV) nDsbDred is available for reduction of its periplasmic partners CcmG and DsbC while cDsbDox is available for reduction by tmDsbDred (see reference 1).



Figure 2: (left) The X-ray structure of lysozyme from bacteriophage lambda shows two different conformations for the lower (51-60) and upper (128-141) lip residues (shown in red) in the unit cell (Evrard et al. JMB 276, 151-64 1998). (right) Reduced 1H-15N heteronuclear NOE values are observed for these residues suggesting that, in solution, the two conformations observed in the crystal interconvert on a fast, picosecond to nanasecond, timescale (see reference 2).