Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I
Respiratory complex I performs the reduction of quinone (Q) to quinol (QH2) and pumps protons across the membrane. Structural data on complex I have provided spectacular insights into the electron and proton transfer paths, as well as into the long (~30 Å) and unique substrate binding channel. Howev...
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| Formaat: | Artikel |
| Taal: | English |
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Frontiers Media S.A.
2019-04-01
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| Reeks: | Frontiers in Chemistry |
| Onderwerpen: | |
| Online toegang: | https://www.frontiersin.org/article/10.3389/fchem.2019.00221/full |
| _version_ | 1828375655491829760 |
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| author | Outi Haapanen Amina Djurabekova Vivek Sharma Vivek Sharma |
| author_facet | Outi Haapanen Amina Djurabekova Vivek Sharma Vivek Sharma |
| author_sort | Outi Haapanen |
| collection | DOAJ |
| description | Respiratory complex I performs the reduction of quinone (Q) to quinol (QH2) and pumps protons across the membrane. Structural data on complex I have provided spectacular insights into the electron and proton transfer paths, as well as into the long (~30 Å) and unique substrate binding channel. However, due to missing structural information on Q binding modes, it remains unclear how Q reduction drives long range (~20 nm) redox-coupled proton pumping in complex I. Here we applied multiscale computational approaches to study the dynamics and redox chemistry of Q and QH2. Based on tens of microseconds of atomistic molecular dynamics (MD) simulations of bacterial and mitochondrial complex I, we find that the dynamics of Q is remarkably rapid and it diffuses from the N2 binding site to another stable site near the entrance of the Q channel in microseconds. Analysis of simulation trajectories also reveal the presence of yet another Q binding site 25–30 Å from the N2 center, which is in remarkable agreement with the electron density observed in recent cryo electron microscopy structure of complex I from Yarrowia lipolytica. Quantum chemical computations on the two Q binding sites closer to the entrance of the Q tunnel reveal redox-coupled protonation reactions that may be important in driving the proton pump of complex I. |
| first_indexed | 2024-04-14T07:50:01Z |
| format | Article |
| id | doaj.art-1882a72b4cda4ec9a28b51e89089a10b |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-14T07:50:01Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-1882a72b4cda4ec9a28b51e89089a10b2022-12-22T02:05:13ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462019-04-01710.3389/fchem.2019.00221449671Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex IOuti Haapanen0Amina Djurabekova1Vivek Sharma2Vivek Sharma3Department of Physics, University of Helsinki, Helsinki, FinlandDepartment of Physics, University of Helsinki, Helsinki, FinlandDepartment of Physics, University of Helsinki, Helsinki, FinlandInstitute of Biotechnology, University of Helsinki, Helsinki, FinlandRespiratory complex I performs the reduction of quinone (Q) to quinol (QH2) and pumps protons across the membrane. Structural data on complex I have provided spectacular insights into the electron and proton transfer paths, as well as into the long (~30 Å) and unique substrate binding channel. However, due to missing structural information on Q binding modes, it remains unclear how Q reduction drives long range (~20 nm) redox-coupled proton pumping in complex I. Here we applied multiscale computational approaches to study the dynamics and redox chemistry of Q and QH2. Based on tens of microseconds of atomistic molecular dynamics (MD) simulations of bacterial and mitochondrial complex I, we find that the dynamics of Q is remarkably rapid and it diffuses from the N2 binding site to another stable site near the entrance of the Q channel in microseconds. Analysis of simulation trajectories also reveal the presence of yet another Q binding site 25–30 Å from the N2 center, which is in remarkable agreement with the electron density observed in recent cryo electron microscopy structure of complex I from Yarrowia lipolytica. Quantum chemical computations on the two Q binding sites closer to the entrance of the Q tunnel reveal redox-coupled protonation reactions that may be important in driving the proton pump of complex I.https://www.frontiersin.org/article/10.3389/fchem.2019.00221/fullredox chemistryproton transportelectron transportdensity functional calculationsmolecular dynamicscell respiration |
| spellingShingle | Outi Haapanen Amina Djurabekova Vivek Sharma Vivek Sharma Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I Frontiers in Chemistry redox chemistry proton transport electron transport density functional calculations molecular dynamics cell respiration |
| title | Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I |
| title_full | Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I |
| title_fullStr | Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I |
| title_full_unstemmed | Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I |
| title_short | Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I |
| title_sort | role of second quinone binding site in proton pumping by respiratory complex i |
| topic | redox chemistry proton transport electron transport density functional calculations molecular dynamics cell respiration |
| url | https://www.frontiersin.org/article/10.3389/fchem.2019.00221/full |
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