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Electron Transfer Coupled to Conformational Dynamics in Cell Respiration

Cellular respiration is a fundamental process required for energy production in many organisms. The terminal electron transfer complex in mitochondrial and many bacterial respiratory chains is cytochrome c oxidase (CcO). This converts the energy released in the cytochrome c/oxygen redox reaction int...

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Autores principales: Reidelbach, Marco, Zimmer, Christoph, Meunier, Brigitte, Rich, Peter R., Sharma, Vivek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378252/
https://www.ncbi.nlm.nih.gov/pubmed/34422907
http://dx.doi.org/10.3389/fmolb.2021.711436
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author Reidelbach, Marco
Zimmer, Christoph
Meunier, Brigitte
Rich, Peter R.
Sharma, Vivek
author_facet Reidelbach, Marco
Zimmer, Christoph
Meunier, Brigitte
Rich, Peter R.
Sharma, Vivek
author_sort Reidelbach, Marco
collection PubMed
description Cellular respiration is a fundamental process required for energy production in many organisms. The terminal electron transfer complex in mitochondrial and many bacterial respiratory chains is cytochrome c oxidase (CcO). This converts the energy released in the cytochrome c/oxygen redox reaction into a transmembrane proton electrochemical gradient that is used subsequently to power ATP synthesis. Despite detailed knowledge of electron and proton transfer paths, a central question remains as to whether the coupling between electron and proton transfer in mammalian mitochondrial forms of CcO is mechanistically equivalent to its bacterial counterparts. Here, we focus on the conserved span between H376 and G384 of transmembrane helix (TMH) X of subunit I. This conformationally-dynamic section has been suggested to link the redox activity with the putative H pathway of proton transfer in mammalian CcO. The two helix X mutants, Val380Met (V380M) and Gly384Asp (G384D), generated in the genetically-tractable yeast CcO, resulted in a respiratory-deficient phenotype caused by the inhibition of intra-protein electron transfer and CcO turnover. Molecular aspects of these variants were studied by long timescale atomistic molecular dynamics simulations performed on wild-type and mutant bovine and yeast CcOs. We identified redox- and mutation-state dependent conformational changes in this span of TMH X of bovine and yeast CcOs which strongly suggests that this dynamic module plays a key role in optimizing intra-protein electron transfers.
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spelling pubmed-83782522021-08-21 Electron Transfer Coupled to Conformational Dynamics in Cell Respiration Reidelbach, Marco Zimmer, Christoph Meunier, Brigitte Rich, Peter R. Sharma, Vivek Front Mol Biosci Molecular Biosciences Cellular respiration is a fundamental process required for energy production in many organisms. The terminal electron transfer complex in mitochondrial and many bacterial respiratory chains is cytochrome c oxidase (CcO). This converts the energy released in the cytochrome c/oxygen redox reaction into a transmembrane proton electrochemical gradient that is used subsequently to power ATP synthesis. Despite detailed knowledge of electron and proton transfer paths, a central question remains as to whether the coupling between electron and proton transfer in mammalian mitochondrial forms of CcO is mechanistically equivalent to its bacterial counterparts. Here, we focus on the conserved span between H376 and G384 of transmembrane helix (TMH) X of subunit I. This conformationally-dynamic section has been suggested to link the redox activity with the putative H pathway of proton transfer in mammalian CcO. The two helix X mutants, Val380Met (V380M) and Gly384Asp (G384D), generated in the genetically-tractable yeast CcO, resulted in a respiratory-deficient phenotype caused by the inhibition of intra-protein electron transfer and CcO turnover. Molecular aspects of these variants were studied by long timescale atomistic molecular dynamics simulations performed on wild-type and mutant bovine and yeast CcOs. We identified redox- and mutation-state dependent conformational changes in this span of TMH X of bovine and yeast CcOs which strongly suggests that this dynamic module plays a key role in optimizing intra-protein electron transfers. Frontiers Media S.A. 2021-08-06 /pmc/articles/PMC8378252/ /pubmed/34422907 http://dx.doi.org/10.3389/fmolb.2021.711436 Text en Copyright © 2021 Reidelbach, Zimmer, Meunier, Rich and Sharma. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Reidelbach, Marco
Zimmer, Christoph
Meunier, Brigitte
Rich, Peter R.
Sharma, Vivek
Electron Transfer Coupled to Conformational Dynamics in Cell Respiration
title Electron Transfer Coupled to Conformational Dynamics in Cell Respiration
title_full Electron Transfer Coupled to Conformational Dynamics in Cell Respiration
title_fullStr Electron Transfer Coupled to Conformational Dynamics in Cell Respiration
title_full_unstemmed Electron Transfer Coupled to Conformational Dynamics in Cell Respiration
title_short Electron Transfer Coupled to Conformational Dynamics in Cell Respiration
title_sort electron transfer coupled to conformational dynamics in cell respiration
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378252/
https://www.ncbi.nlm.nih.gov/pubmed/34422907
http://dx.doi.org/10.3389/fmolb.2021.711436
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