Cryo-EM structures provide insight into how E. coli F₁F_o ATP synthase accommodates symmetry mismatch.

Abstract

F₁F_o 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 F_o 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 F_o 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 F_o motors. We also identify density likely corresponding to lipid molecules that may contribute to the rotor/stator interaction within the F_o motor.