WALKER, JOHN E.

walker@mrc-dunn.cam.ac.uk

Director of the Medical Research Council Dunn Human Nutrition Unit , Cambridge, United Kingdom.

Research interests :
During the DNA sequencing of the genomes of human and bovine mitochondria, he became interested in the enzymes of oxidative phosphorylation. Therefore, since 1978, he has concentrated on studying the structures and functions of the ATP synthase (in bacteria, chloroplasts and mitochondria), and complex I (NADH: ubiquinone oxidoreductase) from mitochondria. Since 1986, he has also collaborated closely with the group of Ferdinando Palmieri at the University of Bari in Italy in studying a family of metabolite transport proteins in the inner membranes of mitochondria.

In 1998, he left the LMB to become the Director of the MRC's Dunn Human Nutrition Unit in Cambridge. One of his aims as Director is to combine traditional methods of studying nutrition with molecular, cellular and genetic approaches to study the fundamental bases of nutritional processes in man, and also to apply them to nutritional problems.

He also retains a long interest in mass spectrometric methods for analysing proteins dating from my period as a D. Phil. student at Oxford University in the late 1960s, continued in a post-doctoral stint in Paris in the early 1970s, and reawakened in our studies of complex I in the early 1990s.

Prizes :
1997 Nobel Laureate in Chemistry "for elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)"

Selected publications :
2001
Palmieri, L., Agrimi, G., Runswick, M.J., Fearnley, I.M., Palmieri, F. & Walker, J.E. Identification in Saccharomyces cerevisiae of two isoforms of a novel mitochondrial transporter for 2-oxoadipate and 2-oxoglutarate. J. Biol. Chem. 276, 1916-1922.

Dolce, V., Fiermonte, G., Runswick, M.J., Palmieri, F. & Walker, J.E. The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals. Proc. Natl. Acad. Sci. USA 98, 2284-2288.

Fiermonte, G., Dolce, V., Palmieri, L., Ventura, M., Runswick, M.J., Palmieri, F. & Walker, J.E. Identification of the human mitochondrial oxodicarboxylate carrier. J. Biol. Chem. 276, 8225-8230.

Menz, R.I., Leslie, A.G.W. & Walker, J.E. The structure and nucleotide occupancy of bovine mitochondrial F1-ATPase are not influenced by crystallisation at high concentrations of nucleotide. FEBS Lett. 494, 11-14.

2000
Sazanov, L.A. & Walker, J.E. Cryo-electron crystallography of two sub-complexes of bovine complex I reveals the relationship between the membrane and peripheral arms. J. Mol. Biol. 302, 455-464.

Gibbons, C., Montgomery, M.G. Leslie, A.G.W. & Walker, J.E. The structure of the central stalk in bovine F1-ATPase at 2.4 Å resolution. Nature Struct. Biol. 7, 1055-1061.

Cabezon, E., Arrechaga, I., Butler, P.J.G. & Walker, J.E. Dimerization of bovine F1-ATPase by binding the inhibitor protein, IF1. J. Biol. Chem. 275, 28353-28355.

Cabezon, E., Butler, P.J., Runswick, M.J. & Walker J.E. Modulation of the oligomerization state of the bovine F1-ATPase inhibitor protein, IF1, by pH. J. Biol. Chem. 275, 25460-25464.

Sazanov, L., Peak-Chew, S.Y., Fearnley, I.M. & Walker, J.E. Resolution of the membrane domain of bovine complex I into subcomplexes: implications for the structural organization of the enzyme. Biochemistry 39, 7229-7235.

Palmieri, L., Runswick, M.J., Fiermonte, G., Walker, J.E. & Palmieri, F. Yeast mitochondrial carriers: bacterial expression, biochemical identification and metabolic significance. J. Bioenerget. Biomembranes 32 , 67-77.

Braig, K., Menz, R.I., Montgomery, M.G., Leslie, A.G. & Walker, J.E. Structure of bovine mitochondrial F(1)-ATPase inhibited by Mg(2+) ADP and aluminium fluoride. Structure 8, 567-573.

Leslie, A.G.W. & Walker, J.E. Structural model of F1-ATPase and the implications for rotary catalysis. Phil. Trans. Roy. Soc. Lond. B 355, 465-472.