1. Structural Biology and Molecular Biophysics

Functional asymmetry and electron flow in the bovine respirasome

  1. Joana S Sousa
  2. Deryck J Mills
  3. Janet Vonck
  4. Werner Kühlbrandt  Is a corresponding author
  1. Max Planck Institute of Biophysics, Germany
https://doi.org/10.7554/eLife.21290
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  1. Joana S Sousa
  2. Deryck J Mills
  3. Janet Vonck
  4. Werner Kühlbrandt
(2016)
Functional asymmetry and electron flow in the bovine respirasome
eLife 5:e21290.
https://doi.org/10.7554/eLife.21290
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Abstract

Respirasomes are macromolecular assemblies of the respiratory chain complexes I, III and IV in the inner mitochondrial membrane. We determined the structure of supercomplex I1III2IV1 from bovine heart mitochondria by cryo-EM at 9 Å resolution. Most protein-protein contacts between complex I, III and IV in the membrane are mediated by supernumerary subunits. Of the two Rieske iron-sulfur cluster domains in the complex III dimer, one is resolved, indicating that this domain is immobile and unable to transfer electrons. The central position of the active complex III monomer between complex I and IV in the respirasome is optimal for accepting reduced quinone from complex I over a short diffusion distance of 11 nm, and delivering reduced cytochrome c to complex IV. The functional asymmetry of complex III provides strong evidence for directed electron flow from complex I to complex IV through the active complex III monomer in the mammalian supercomplex.

Data availability

The following data sets were generated
    1. Sousa JS
    2. Mills DJ
    3. Vonck J
    4. Kuehlbrandt W
    (2016) Cryo-EM map of bovine respirasome
    Publicly available at the EBI Protein Data Bank (accession no: EMD-4107).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-4107
    1. Sousa JS
    2. Mills DJ
    3. Vonck J
    4. Kuehlbrandt W
    (2016) Cryo-EM of bovine respirasome
    Publicly available at th EBI Protein Data Bank (accession no: EMD-4108).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-4108
    1. Sousa JS
    2. Mills DJ
    3. Vonck J
    4. Kuehlbrandt W
    (2016) Cryo-EM of bovine respirasome
    Publicly available at the EBI Protein Data Bank (accession no: EMD-4109).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-4109
    1. Sousa JS
    2. Mills DJ
    3. Vonck J
    4. Kuehlbrandt W
    (2016) cryo-EM of bovine respirasome
    Publicly available at the RCSB Protein Data Bank (accession no: 5LUF).
    http://www.rcsb.org/pdb/explore.do?structureId=5LUF
The following previously published data sets were used
    1. Vinothkumar KR
    2. Zhu J
    3. Hirst J
    (2014) Electron cryo-microscopy of bovine Complex I
    Publicly available at the EBI Protein Data Bank (accession no: EMD-4109).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-4109

Article and author information

Author details

  1. Joana S Sousa

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany
    Competing interests
    No competing interests declared.

  2. Deryck J Mills

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany
    Competing interests
    No competing interests declared.

  3. Janet Vonck

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5659-8863

  4. Werner Kühlbrandt

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany
    For correspondence
    werner.kuehlbrandt@biophys.mpg.de
    Competing interests
    Werner Kühlbrandt, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2013-4810

Funding

Max-Planck-Gesellschaft

  • Werner Kühlbrandt

Cluster of Excellence Frankfurt

  • Werner Kühlbrandt

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

Reviewing Editor

  1. Stephen C. Harrison, Harvard Medical School, United States

Version history

  1. Received: September 5, 2016
  2. Accepted: November 3, 2016
  3. Accepted Manuscript published: November 10, 2016 (version 1)
  4. Version of Record published: November 21, 2016 (version 2)

Copyright

© 2016, Sousa 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. Joana S Sousa
  2. Deryck J Mills
  3. Janet Vonck
  4. Werner Kühlbrandt
(2016)
Functional asymmetry and electron flow in the bovine respirasome
eLife 5:e21290.
https://doi.org/10.7554/eLife.21290

Share this article

https://doi.org/10.7554/eLife.21290

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