Redox-coupled quinone dynamics in the respiratory complex I

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Warnau , J , Sharma , V , Gamiz-Hernandez , A P , Di Luca , A , Haapanen , O , Vattulainen , I , Wikström , M , Hummer , G & Kaila , V R I 2018 , ' Redox-coupled quinone dynamics in the respiratory complex I ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 115 , no. 36 , pp. E8413-E8420 .

Title: Redox-coupled quinone dynamics in the respiratory complex I
Author: Warnau, Judith; Sharma, Vivek; Gamiz-Hernandez, Ana P.; Di Luca, Andrea; Haapanen, Outi; Vattulainen, Ilpo; Wikström, Mårten; Hummer, Gerhard; Kaila, Ville R. I.
Contributor organization: Department of Physics
Institute of Biotechnology
Date: 2018-09-04
Language: eng
Number of pages: 8
Belongs to series: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
Abstract: Complex I couples the free energy released from quinone (Q) reduction to pump protons across the biological membrane in the respiratory chains of mitochondria and many bacteria. The Q reduction site is separated by a large distance from the proton-pumping membrane domain. To address the molecular mechanism of this long-range proton-electron coupling, we perform here full atomistic molecular dynamics simulations, free energy calculations, and continuum electrostatics calculations on complex I from Thermus thermophilus. We show that the dynamics of Q is redox-state-dependent, and that quinol, QH(2), moves out of its reduction site and into a site in the Q tunnel that is occupied by a Q analog in a crystal structure of Yarrowia lipolytica. We also identify a second Q-binding site near the opening of the Q tunnel in the membrane domain, where the Q headgroup forms strong interactions with a cluster of aromatic and charged residues, while the Q tail resides in the lipid membrane. We estimate the effective diffusion coefficient of Q in the tunnel, and in turn the characteristic time for Q to reach the active site and for QH2 to escape to the membrane. Our simulations show that Q moves along the Q tunnel in a redox-state-dependent manner, with distinct binding sites formed by conserved residue clusters. The motion of Q to these binding sites is proposed to be coupled to the proton-pumping machinery in complex I.
Subject: NADH: ubiquinone oxidoreductase
diffusion model
electron transfer
molecular simulations
cell respiration
114 Physical sciences
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion
Funder: Valtion perusrahoitus/hankkeet
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