1. Evolutionary Biology
  2. Structural Biology and Molecular Biophysics

Structure of a mitochondrial ATP synthase with bound native cardiolipin

  1. Alexander Mühleip
  2. Sarah E McComas
  3. Alexey Amunts  Is a corresponding author
  1. Stockholm University, Sweden
https://doi.org/10.7554/eLife.51179
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  1. Alexander Mühleip
  2. Sarah E McComas
  3. Alexey Amunts
(2019)
Structure of a mitochondrial ATP synthase with bound native cardiolipin
eLife 8:e51179.
https://doi.org/10.7554/eLife.51179
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Abstract

The mitochondrial ATP synthase fuels eukaryotic cells with chemical energy. Here we report the cryo-EM structure of a divergent ATP synthase dimer from mitochondria of Euglena gracilis, a member of the phylum Euglenozoa that also includes human parasites. It features 29 different subunits, 8 of which are newly identified. The membrane region was determined to 2.8 Å resolution, enabling the identification of 37 associated lipids, including 25 cardiolipins, which provides insight into protein-lipid interaction and their functional roles. The rotor-stator interface comprises four membrane-embedded horizontal helices, including a distinct subunit a. The dimer interface is formed entirely by phylum-specific components, and a peripherally associated subcomplex contributes to the membrane curvature. The central and peripheral stalks directly interact with each other. Last, the ATPase inhibitory factor 1 (IF1) binds in a mode that is different from human, but conserved in Trypanosomatids.

Data availability

All data generated or analyzed during this study are included in this Article and the Supplementary Information. The cryo-EM maps have been deposited in the Electron Microscopy Data Bank with accession codes EMD-10467, EMD-10468, EMD-10469, EMD-10470, EMD 10471, EMD-10472, EMD-10473, EMD-10474, EMD-10475. The atomic models have been deposited in the Protein Data Bank under accession codes 6TDU, 6TDV, 6TDW, 6TDX, 6TDY, 6TDZ, 6TE0.

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The following previously published data sets were used

Article and author information

Author details

  1. Alexander Mühleip

    Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  2. Sarah E McComas

    Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  3. Alexey Amunts

    Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden
    For correspondence
    amunts@scilifelab.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5302-1740

Funding

Stiftelsen för Strategisk Forskning (FFL15:0325)

  • Alexey Amunts

Ragnar Söderbergs stiftelse (M44/16)

  • Alexey Amunts

Vetenskapsrådet (NT_2015-04107)

  • Alexey Amunts

Cancerfonden (2017/1041)

  • Alexey Amunts

H2020 European Research Council (ERC-2018-StG-805230)

  • Alexey Amunts

Knut och Alice Wallenbergs Stiftelse ((2018.0080)

  • Alexey Amunts

European Molecular Biology Organization (ALTF 260-2017)

  • Alexander Mühleip

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Andrew P Carter, MRC Laboratory of Molecular Biology, United Kingdom

Version history

  1. Received: August 18, 2019
  2. Accepted: November 16, 2019
  3. Accepted Manuscript published: November 18, 2019 (version 1)
  4. Version of Record published: December 24, 2019 (version 2)

Copyright

© 2019, Mühleip et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Alexander Mühleip
  2. Sarah E McComas
  3. Alexey Amunts
(2019)
Structure of a mitochondrial ATP synthase with bound native cardiolipin
eLife 8:e51179.
https://doi.org/10.7554/eLife.51179

Share this article

https://doi.org/10.7554/eLife.51179

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