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...

Cijeli opis

Bibliografski detalji
Glavni autori: Outi Haapanen, Amina Djurabekova, Vivek Sharma
Format: Članak
Jezik:English
Izdano: Frontiers Media S.A. 2019-04-01
Serija:Frontiers in Chemistry
Teme:
Online pristup:https://www.frontiersin.org/article/10.3389/fchem.2019.00221/full
_version_ 1828375655491829760
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
work_keys_str_mv AT outihaapanen roleofsecondquinonebindingsiteinprotonpumpingbyrespiratorycomplexi
AT aminadjurabekova roleofsecondquinonebindingsiteinprotonpumpingbyrespiratorycomplexi
AT viveksharma roleofsecondquinonebindingsiteinprotonpumpingbyrespiratorycomplexi
AT viveksharma roleofsecondquinonebindingsiteinprotonpumpingbyrespiratorycomplexi