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Science. 2018 May 11;360(6389). pii: eaas9699. doi: 10.1126/science.aas9699. Epub 2018 Apr 12.

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

Author information

1
Department of Biological Chemistry and Molecular Biology, Chicago Medical School, Rosalind Franklin University, 3333 Green Bay Road, North Chicago, IL 60064, USA.
2
Department of Cell Biology, Harvard Medical School, 250 Longwood Avenue, SGM 509, Boston, MA 02115, USA.
3
Theoretical Molecular Biophysics Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA.
4
Department of Cell Biology, Harvard Medical School, 250 Longwood Avenue, SGM 509, Boston, MA 02115, USA. david.mueller@rosalindfranklin.edu maofu_liao@hms.harvard.edu.
5
Department of Biological Chemistry and Molecular Biology, Chicago Medical School, Rosalind Franklin University, 3333 Green Bay Road, North Chicago, IL 60064, USA. david.mueller@rosalindfranklin.edu maofu_liao@hms.harvard.edu.

Abstract

Mitochondrial adenosine triphosphate (ATP) synthase comprises a membrane embedded Fo 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 Fo c10-ring in the direction of ATP synthesis, relative to the structure of isolated Fo Our cryo-EM structures show how F1 and Fo are coupled, give insight into the proton translocation pathway, and show how oligomycin blocks ATP synthesis.

PMID:
29650704
PMCID:
PMC5948177
DOI:
10.1126/science.aas9699
[Indexed for MEDLINE]
Free PMC Article

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