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

Elife. 2015 Oct 6:4:e10180. doi: 10.7554/eLife.10180.


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 FO 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 FO 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 FO region support a Brownian ratchet mechanism for proton-translocation-driven rotation in ATP synthases.

Keywords: ATP synthase; biochemistry; biophysics; bovine; coevolution; cryo-EM; evolutionary covariance; structural biology; structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Computational Biology
  • Cryoelectron Microscopy*
  • Imaging, Three-Dimensional
  • Mitochondrial Proton-Translocating ATPases / chemistry*
  • Mitochondrial Proton-Translocating ATPases / genetics
  • Models, Molecular
  • Protein Conformation
  • Protein Folding


  • Mitochondrial Proton-Translocating ATPases