Cryo-EM structure of the entire mammalian F-type ATP synthase

G. Pinke, L. Zhou, L.A. Sazanov, Nature Structural and Molecular Biology (2020).

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Abstract
The majority of adenosine triphosphate (ATP) powering cellular processes in eukaryotes is produced by the mitochondrial F1Fo ATP synthase. Here, we present the atomic models of the membrane Fo domain and the entire mammalian (ovine) F1Fo, determined by cryo-electron microscopy. Subunits in the membrane domain are arranged in the ‘proton translocation cluster’ attached to the c-ring and a more distant ‘hook apparatus’ holding subunit e. Unexpectedly, this subunit is anchored to a lipid ‘plug’ capping the c-ring. We present a detailed proton translocation pathway in mammalian Fo and key inter-monomer contacts in F1Fo multimers. Cryo-EM maps of F1Fo exposed to calcium reveal a retracted subunit e and a disassembled c-ring, suggesting permeability transition pore opening. We propose a model for the permeability transition pore opening, whereby subunit e pulls the lipid plug out of the c-ring. Our structure will allow the design of drugs for many emerging applications in medicine.
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Date Published
2020-09-14
Journal Title
Nature Structural and Molecular Biology
Acknowledgement
We thank J. Novacek from CEITEC (Brno, Czech Republic) for assistance with collecting the FEI Krios dataset and iNEXT for providing access to CEITEC. We thank the IST Austria EM facility for access and assistance with collecting the FEI Glacios dataset. Data processing was performed at the IST high-performance computing cluster. This work has been supported by iNEXT EM HEDC (proposal 4506), funded by the Horizon 2020 Programme of the European Commission.
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Pinke G, Zhou L, Sazanov LA. Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology. 2020. doi:10.1038/s41594-020-0503-8
Pinke, G., Zhou, L., & Sazanov, L. A. (2020). Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology. https://doi.org/10.1038/s41594-020-0503-8
Pinke, Gergely, Long Zhou, and Leonid A Sazanov. “Cryo-EM Structure of the Entire Mammalian F-Type ATP Synthase.” Nature Structural and Molecular Biology, 2020. https://doi.org/10.1038/s41594-020-0503-8.
G. Pinke, L. Zhou, and L. A. Sazanov, “Cryo-EM structure of the entire mammalian F-type ATP synthase,” Nature Structural and Molecular Biology, 2020.
Pinke G, Zhou L, Sazanov LA. 2020. Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology.
Pinke, Gergely, et al. “Cryo-EM Structure of the Entire Mammalian F-Type ATP Synthase.” Nature Structural and Molecular Biology, Springer Nature, 2020, doi:10.1038/s41594-020-0503-8.
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