Cryo-EM structures provide insight into how E. coli F1Fo ATP synthase accommodates symmetry mismatch

Nat Commun. 2020 May 26;11(1):2615. doi: 10.1038/s41467-020-16387-2.


F1Fo ATP synthase functions as a biological rotary generator that makes a major contribution to cellular energy production. It comprises two molecular motors coupled together by a central and a peripheral stalk. Proton flow through the Fo motor generates rotation of the central stalk, inducing conformational changes in the F1 motor that catalyzes ATP production. Here we present nine cryo-EM structures of E. coli ATP synthase to 3.1-3.4 Å resolution, in four discrete rotational sub-states, which provide a comprehensive structural model for this widely studied bacterial molecular machine. We observe torsional flexing of the entire complex and a rotational sub-step of Fo associated with long-range conformational changes that indicates how this flexibility accommodates the mismatch between the 3- and 10-fold symmetries of the F1 and Fo motors. We also identify density likely corresponding to lipid molecules that may contribute to the rotor/stator interaction within the Fo motor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Cryoelectron Microscopy
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Lipids / chemistry
  • Models, Molecular
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Proton-Translocating ATPases / chemistry*
  • Proton-Translocating ATPases / metabolism
  • Rotation
  • Structure-Activity Relationship


  • Escherichia coli Proteins
  • Lipids
  • Protein Subunits
  • Adenosine Diphosphate
  • Proton-Translocating ATPases