Functional asymmetry and electron flow in the bovine respirasome

Abstract
Data availability
Article and author information

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

(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
(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
(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
(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

(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
1. Iwata S
2. Lee JW
3. Okada K
4. Lee JK
5. Iwata M
6. Rasmussen B
7. Link TA
8. Ramaswamy S
9. Jap BK
(1999) CYTOCHROME BC1 COMPLEX FROM BOVINE
Publicly available at the RCSB Protein Data Bank (accession no: 1BGY).

http://www.rcsb.org/pdb/explore.do?structureId=1BGY
(1996) STRUCTURE OF BOVINE HEART CYTOCHROME C OXIDASE AT THE FULLY OXIDIZED STATE
Publicly available at the RCSB Protein Data Bank (accession no: 1OCC).

http://www.rcsb.org/pdb/explore.do?structureId=1occ

Article and author information

Author details

Joana S Sousa

Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany

Competing interests
No competing interests declared.
Deryck J Mills

Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany

Competing interests
No competing interests declared.
Janet Vonck

Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-5659-8863
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.

"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.

Copyright

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.