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Respiratory complex I with charge symmetry in the membrane arm pumps protons
Energy-converting NADH:ubiquinone oxidoreductase, respiratory complex I, is essential for cellular energy metabolism coupling NADH oxidation to proton translocation. The mechanism of proton translocation by complex I is still under debate. Its membrane arm contains an unusual central axis of polar a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271201/ https://www.ncbi.nlm.nih.gov/pubmed/35759670 http://dx.doi.org/10.1073/pnas.2123090119 |
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author | Hoeser, Franziska Tausend, Hannes Götz, Sinja Wohlwend, Daniel Einsle, Oliver Günther, Stefan Friedrich, Thorsten |
author_facet | Hoeser, Franziska Tausend, Hannes Götz, Sinja Wohlwend, Daniel Einsle, Oliver Günther, Stefan Friedrich, Thorsten |
author_sort | Hoeser, Franziska |
collection | PubMed |
description | Energy-converting NADH:ubiquinone oxidoreductase, respiratory complex I, is essential for cellular energy metabolism coupling NADH oxidation to proton translocation. The mechanism of proton translocation by complex I is still under debate. Its membrane arm contains an unusual central axis of polar and charged amino acid residues connecting the quinone binding site with the antiporter-type subunits NuoL, NuoM, and NuoN, proposed to catalyze proton translocation. Quinone chemistry probably causes conformational changes and electrostatic interactions that are propagated through these subunits by a conserved pattern of predominantly lysine, histidine, and glutamate residues. These conserved residues are thought to transfer protons along and across the membrane arm. The distinct charge distribution in the membrane arm is a prerequisite for proton translocation. Remarkably, the central subunit NuoM contains a conserved glutamate residue in a position that is taken by a lysine residue in the two other antiporter-type subunits. It was proposed that this charge asymmetry is essential for proton translocation, as it should enable NuoM to operate asynchronously with NuoL and NuoN. Accordingly, we exchanged the conserved glutamate in NuoM for a lysine residue, introducing charge symmetry in the membrane arm. The stably assembled variant pumps protons across the membrane, but with a diminished H(+)/e(−) stoichiometry of 1.5. Thus, charge asymmetry is not essential for proton translocation by complex I, casting doubts on the suggestion of an asynchronous operation of NuoL, NuoM, and NuoN. Furthermore, our data emphasize the importance of a balanced charge distribution in the protein for directional proton transfer. |
format | Online Article Text |
id | pubmed-9271201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-92712012022-07-11 Respiratory complex I with charge symmetry in the membrane arm pumps protons Hoeser, Franziska Tausend, Hannes Götz, Sinja Wohlwend, Daniel Einsle, Oliver Günther, Stefan Friedrich, Thorsten Proc Natl Acad Sci U S A Biological Sciences Energy-converting NADH:ubiquinone oxidoreductase, respiratory complex I, is essential for cellular energy metabolism coupling NADH oxidation to proton translocation. The mechanism of proton translocation by complex I is still under debate. Its membrane arm contains an unusual central axis of polar and charged amino acid residues connecting the quinone binding site with the antiporter-type subunits NuoL, NuoM, and NuoN, proposed to catalyze proton translocation. Quinone chemistry probably causes conformational changes and electrostatic interactions that are propagated through these subunits by a conserved pattern of predominantly lysine, histidine, and glutamate residues. These conserved residues are thought to transfer protons along and across the membrane arm. The distinct charge distribution in the membrane arm is a prerequisite for proton translocation. Remarkably, the central subunit NuoM contains a conserved glutamate residue in a position that is taken by a lysine residue in the two other antiporter-type subunits. It was proposed that this charge asymmetry is essential for proton translocation, as it should enable NuoM to operate asynchronously with NuoL and NuoN. Accordingly, we exchanged the conserved glutamate in NuoM for a lysine residue, introducing charge symmetry in the membrane arm. The stably assembled variant pumps protons across the membrane, but with a diminished H(+)/e(−) stoichiometry of 1.5. Thus, charge asymmetry is not essential for proton translocation by complex I, casting doubts on the suggestion of an asynchronous operation of NuoL, NuoM, and NuoN. Furthermore, our data emphasize the importance of a balanced charge distribution in the protein for directional proton transfer. National Academy of Sciences 2022-06-27 2022-07-05 /pmc/articles/PMC9271201/ /pubmed/35759670 http://dx.doi.org/10.1073/pnas.2123090119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Hoeser, Franziska Tausend, Hannes Götz, Sinja Wohlwend, Daniel Einsle, Oliver Günther, Stefan Friedrich, Thorsten Respiratory complex I with charge symmetry in the membrane arm pumps protons |
title | Respiratory complex I with charge symmetry in the membrane arm pumps protons |
title_full | Respiratory complex I with charge symmetry in the membrane arm pumps protons |
title_fullStr | Respiratory complex I with charge symmetry in the membrane arm pumps protons |
title_full_unstemmed | Respiratory complex I with charge symmetry in the membrane arm pumps protons |
title_short | Respiratory complex I with charge symmetry in the membrane arm pumps protons |
title_sort | respiratory complex i with charge symmetry in the membrane arm pumps protons |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271201/ https://www.ncbi.nlm.nih.gov/pubmed/35759670 http://dx.doi.org/10.1073/pnas.2123090119 |
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