Reidelbach, M;
Zimmer, C;
Meunier, B;
Rich, PR;
Sharma, V;
(2021)
Electron Transfer Coupled to Conformational Dynamics in Cell Respiration.
Frontiers in Molecular Biosciences
, 8
, Article 711436. 10.3389/fmolb.2021.711436.
Preview |
Text
Rich_fmolb-08-711436.pdf - Published Version Download (2MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | Electron Transfer Coupled to Conformational Dynamics in Cell Respiration |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fmolb.2021.711436 |
| Publisher version: | https://doi.org/10.3389/fmolb.2021.711436 |
| Language: | English |
| Additional information: | © 2021 Reidelbach, Zimmer, Meunier, Rich and Sharma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). |
| Keywords: | proton pumping, molecular dynamics simulations, density functional theory, yeast bioenergetics, mitochondrial respiration |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10137614 |
Archive Staff Only
 |
View Item |
