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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...

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Autores principales: Hoeser, Franziska, Tausend, Hannes, Götz, Sinja, Wohlwend, Daniel, Einsle, Oliver, Günther, Stefan, Friedrich, Thorsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
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.
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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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