Functional asymmetry and electron flow in the bovine respirasome
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
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Cryo-EM map of bovine respirasomePublicly available at the EBI Protein Data Bank (accession no: EMD-4107).
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Cryo-EM of bovine respirasomePublicly available at th EBI Protein Data Bank (accession no: EMD-4108).
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Cryo-EM of bovine respirasomePublicly available at the EBI Protein Data Bank (accession no: EMD-4109).
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cryo-EM of bovine respirasomePublicly available at the RCSB Protein Data Bank (accession no: 5LUF).
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Electron cryo-microscopy of bovine Complex IPublicly available at the EBI Protein Data Bank (accession no: EMD-4109).
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CYTOCHROME BC1 COMPLEX FROM BOVINEPublicly available at the RCSB Protein Data Bank (accession no: 1BGY).
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STRUCTURE OF BOVINE HEART CYTOCHROME C OXIDASE AT THE FULLY OXIDIZED STATEPublicly available at the RCSB Protein Data Bank (accession no: 1OCC).
Article and author information
Author details
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
- Stephen C. Harrison, Harvard Medical School, United States
Version history
- Received: September 5, 2016
- Accepted: November 3, 2016
- Accepted Manuscript published: November 10, 2016 (version 1)
- 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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