PMID- 34422907
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210824
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 8
DP  - 2021
TI  - Electron Transfer Coupled to Conformational Dynamics in Cell Respiration.
PG  - 711436
LID - 10.3389/fmolb.2021.711436 [doi]
LID - 711436
AB  - 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.
CI  - Copyright (c) 2021 Reidelbach, Zimmer, Meunier, Rich and Sharma.
FAU - Reidelbach, Marco
AU  - Reidelbach M
AD  - Department of Physics, University of Helsinki, Helsinki, Finland.
FAU - Zimmer, Christoph
AU  - Zimmer C
AD  - Department of Structural and Molecular Biology, University College London, 
      London, United Kingdom.
FAU - Meunier, Brigitte
AU  - Meunier B
AD  - Institute for Integrative Biology of the Cell (I2BC), Universite Paris-Saclay, 
      Gif-sur-Yvette, France.
FAU - Rich, Peter R
AU  - Rich PR
AD  - Department of Structural and Molecular Biology, University College London, 
      London, United Kingdom.
FAU - Sharma, Vivek
AU  - Sharma V
AD  - Department of Physics, University of Helsinki, Helsinki, Finland.
AD  - HiLIFE Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
LA  - eng
PT  - Journal Article
DEP - 20210806
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC8378252
OTO - NOTNLM
OT  - density functional theory
OT  - mitochondrial respiration
OT  - molecular dynamics simulations
OT  - proton pumping
OT  - yeast bioenergetics
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/08/24 06:00
MHDA- 2021/08/24 06:01
PMCR- 2021/01/01
CRDT- 2021/08/23 06:37
PHST- 2021/05/18 00:00 [received]
PHST- 2021/07/26 00:00 [accepted]
PHST- 2021/08/23 06:37 [entrez]
PHST- 2021/08/24 06:00 [pubmed]
PHST- 2021/08/24 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 711436 [pii]
AID - 10.3389/fmolb.2021.711436 [doi]
PST - epublish
SO  - Front Mol Biosci. 2021 Aug 6;8:711436. doi: 10.3389/fmolb.2021.711436. 
      eCollection 2021.