High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane

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Abstract

Mitochondrial adenosine triphosphate (ATP) synthase comprises a membrane embedded F_o motor that rotates to drive ATP synthesis in the F₁ subunit. We used single-particle cryo-electron microscopy (cryo-EM) to obtain structures of the full complex in a lipid bilayer in the absence or presence of the inhibitor oligomycin at 3.6- and 3.8-angstrom resolution, respectively. To limit conformational heterogeneity, we locked the rotor in a single conformation by fusing the F6 subunit of the stator with the δ subunit of the rotor. Assembly of the enzyme with the F6-δ fusion caused a twisting of the rotor and a 9° rotation of the F_o c₁₀-ring in the direction of ATP synthesis, relative to the structure of isolated F_o Our cryo-EM structures show how F₁ and F_o are coupled, give insight into the proton translocation pathway, and show how oligomycin blocks ATP synthesis.

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