Rotary substates of mitochondrial ATP synthase reveal the basis of flexible F1-Fo coupling

Science. 2019 Jun 21;364(6446):eaaw9128. doi: 10.1126/science.aaw9128. Epub 2019 Jun 20.


F1Fo-adenosine triphosphate (ATP) synthases make the energy of the proton-motive force available for energy-consuming processes in the cell. We determined the single-particle cryo-electron microscopy structure of active dimeric ATP synthase from mitochondria of Polytomella sp. at a resolution of 2.7 to 2.8 angstroms. Separation of 13 well-defined rotary substates by three-dimensional classification provides a detailed picture of the molecular motions that accompany c-ring rotation and result in ATP synthesis. Crucially, the F1 head rotates along with the central stalk and c-ring rotor for the first ~30° of each 120° primary rotary step to facilitate flexible coupling of the stoichiometrically mismatched F1 and Fo subcomplexes. Flexibility is mediated primarily by the interdomain hinge of the conserved OSCP subunit. A conserved metal ion in the proton access channel may synchronize c-ring protonation with rotation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chlorophyceae / enzymology*
  • Cryoelectron Microscopy
  • Mitochondria / enzymology*
  • Mitochondrial Proton-Translocating ATPases / chemistry*
  • Plant Proteins / chemistry*
  • Protein Conformation
  • Protein Multimerization
  • Proton-Motive Force
  • Rotation


  • Plant Proteins
  • Mitochondrial Proton-Translocating ATPases