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

TitleHigh-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane.
Publication TypeJournal Article
Year of Publication2018
AuthorsSrivastava, AP, Luo, M, Zhou, W, Symersky, J, Bai, D, Chambers, MG, Faraldo-Gómez, JD, Liao, M, Mueller, DM
Date Published2018 05 11
KeywordsAdenosine Triphosphate, Cryoelectron Microscopy, Membrane Lipids, Mitochondrial Membranes, Mitochondrial Proton-Translocating ATPases, Molecular Motor Proteins, Oligomycins, Protein Conformation, Protein Subunits, Saccharomyces cerevisiae Proteins, Single Molecule Imaging

Mitochondrial adenosine triphosphate (ATP) synthase comprises a membrane embedded F motor that rotates to drive ATP synthesis in the F 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 c-ring in the direction of ATP synthesis, relative to the structure of isolated F Our cryo-EM structures show how F and F are coupled, give insight into the proton translocation pathway, and show how oligomycin blocks ATP synthesis.

Alternate JournalScience
Citation Key10.1126/science.aas9699
PubMed ID29650704
PubMed Central IDPMC5948177
Grant ListR01 GM066223 / GM / NIGMS NIH HHS / United States