ATP synthase

Research area: 
Understanding the molecular mechanism of how ATP is made.
Group leader: 
John Walker

In eubacteria, chloroplasts and mitochondria, the synthesis of ATP is carried out by a highly complex molecular machine known as ATP synthase. Our aim is to understand how this machine works. We are concentrating mainly on the enzyme from mitochondria which has many features in common with the bacterial and chloroplast enzymes. It sits in the inner membranes of the organelle, where it uses the transmembrane proton motive force (pmf) generated by the oxidation of nutrients as a source of energy for making ATP. The pmf across the inner membrane of the organelle is coupled to the chemical synthesis of ATP from ADP and phosphate by a rotary mechanism illustrated in the Figure. During ATP synthesis, the central rotor turns in the direction shown about 150 times every second. In order to provide energy to sustain our lives, every day, each one us produces a quantity of ATP by this mechanism that is approximately equal to our body weights.

ATP Synthase animation

Background information

We are solving structures of domains of the ATP synthase complex by X-ray crystallography, and building them up into a mosaic structure within the context of an overall low resolution structure determined by electron microscopy and averaging the images of single particles of the enzyme.

We are examining the structures of the catalytic F1 domain trapped in various states in order to understand the details of the catalytic cycle.

We are attempting to crystalize the intact ATP synthase complex isolated from several species of mitochondria and from eubacteria.

A series of animations showing the architecture and catalytic function of ATP synthase

Selected publications

Andrews, B., Carroll, J., Ding, S., Fearnley, I & Walker, J. (2013).
Assembly factors for the membrane arm of human complex i
Proc. Natl. Acad. Sci. U. S. A., 110, 18934-18939.

Rhein, V. F., Carroll, J., Ding, S., Fearnley, I. M. & Walker., J. E (2013).
NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex i
Journal of Biological Chemistry 288, 33016-33026.

Carroll, J., Ding, S., Fearnley, I. & Walker, J. (2013).
Post-translational modifications near the quinone binding site of mammalian complex I
J. Biol. Chem., pp -.

Baker, L. A., Watt, I. N., Runswick, M. J., Walker, J. E. & Rubinstein, J. L. (2012).
Arrangement of subunits in intact mammalian mitochondrial ATP synthase determined by cryo-EM
Proc. Natl. Acad. Sci. U. S. A., 109, 11675-11680.

Rees, D. M., Montgomery, M. G., Leslie, A. G. W. & Walker, J. E. (2012).
Structural evidence of a new catalytic intermediate in the pathway of ATP hydrolysis by F1-ATPase from bovine heart mitochondria
Proc. Natl. Acad. Sci. U. S. A., 109, 11139-11143.

Watt, I. N., Montgomery, M. G., Runswick, M. J., Leslie, A. G. W. & Walker, J. E. (2010).
Bioenergetic cost of making an adenosine triphosphate molecule in animal mitochondria
Proc. Natl. Acad. Sci. U. S. A., 107, 16823-16827.

Rees, D. M., Leslie, A. G. W. & Walker, J. E. (2009).
The structure of the membrane extrinsic region of bovine ATP synthase
Proc. Natl. Acad. Sci. U. S. A., 106, 21597-21601.

Gledhill, J. R., Montgomery, M. G., Leslie, A. G. W. & Walker, J. E. (2007).
How the regulatory protein, IF1, inhibits F1-ATPase from bovine mitochondria
Proc. Natl. Acad. Sci. U. S. A., 104, 15671-15676.

Gledhill, J. R., Montgomery, M. G., Leslie, A. G. W. & Walker, J. E. (2007).
Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols
Proc. Natl. Acad. Sci. U. S. A., 104, 13632-13637.

Bowler, M. W., Montgomery, M. G., Leslie, A. G. W. & Walker, J. E. (2007).
Ground state structure of F1-ATPase from bovine heart mitochondria at 1.9 Å resolution..
J. Biol. Chem., 282, 14238-14242.