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

PINKE, G., L. ZHOU and L.A. SAZANOV. Cryo-EM structure of the entire mammalian F-type ATP synthase. NATURE STRUCTURAL & MOLECULAR BIOLOGY. NEW YORK: NATURE PUBLISHING GROUP, 2020, vol. 27, No 11, p. 1077-1101. ISSN 1545-9993. Available from: https://dx.doi.org/10.1038/s41594-020-0503-8.

Basic information

• Original name: Cryo-EM structure of the entire mammalian F-type ATP synthase
• Authors: PINKE, G., L. ZHOU and L.A. SAZANOV.
• Edition: NATURE STRUCTURAL & MOLECULAR BIOLOGY, NEW YORK, NATURE PUBLISHING GROUP, 2020, 1545-9993.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: Netherlands
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 15.369
• RIV identification code: RIV/00216224:14740/20:00121456
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1038/s41594-020-0503-8
• UT WoS: 000569299400004
• Keywords in English: MITOCHONDRIAL PERMEABILITY TRANSITION; C-SUBUNIT; COMPLEX I; ATOMIC MODEL; ARCHITECTURE; PREDICTION; CHANNEL; REGION; DIMERS; MOTION
• Tags: ne MU, rivok
• Tags: International impact, Reviewed

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. Cryo-EM structures of the entire mammalian F1Fo ATPase reveal several new features and details on the proton translocation pathway and suggest a model for the opening of the permeability transition pore.

Links

• 90127, large research infrastructures: Name: CIISB II