Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM

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Abstract

Adenosine triphosphate (ATP), the chemical energy currency of biology, is synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP synthases operate by a rotary catalytic mechanism where proton translocation through the membrane-inserted F₀ region is coupled to ATP synthesis in the catalytic F₁ region via rotation of a central rotor subcomplex. We report here single particle electron cryomicroscopy (cryo-EM) analysis of the bovine mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis allowed us to determine the fold of the a subunit, suggesting a proton translocation path through the F₀ region that involves both the a and b subunits. 3D classification of images revealed seven distinct states of the enzyme that show different modes of bending and twisting in the intact ATP synthase. Rotational fluctuations of the c₈-ring within the F₀ region support a Brownian ratchet mechanism for proton-translocation driven rotation in ATP synthases.

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Anna Zhou

The Hospital for Sick Children Research Institute, University of Toronto, Toronto, Canada

Competing interests
The authors declare that no competing interests exist.
Alexis Rohou

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States

Competing interests
The authors declare that no competing interests exist.
Daniel G Schep

The Hospital for Sick Children Research Institute, University of Toronto, Toronto, Canada

Competing interests
The authors declare that no competing interests exist.
John V Bason

MRC Mitochondrial Biology Unit, Medical Research Council, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Martin G Montgomery

MRC Mitochondrial Biology Unit, Medical Research Council, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
John E Walker

MRC Mitochondrial Biology Unit, Medical Research Council, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Nikolaus Grigorieff

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States

Competing interests
The authors declare that no competing interests exist.
John L Rubinstein

The Hospital for Sick Children, University of Toronto, Toronto, Canada

For correspondence
john.rubinstein@utoronto.ca

Competing interests
The authors declare that no competing interests exist.

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