Redox-coupled quinone dynamics in the respiratory complex I

  • 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, QH2, 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.

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Author:Judith Warnau, Vivek Sharma, Ana Patricia L Gámiz-Hernández, Andrea Di Luca, Outi Haapanen, Ilpo Vattulainen, Mårten Wikström, Gerhard HummerORCiD, Ville R. I. Kaila
Pubmed Id:
Parent Title (English):Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Acad. of Sciences
Place of publication:Washington, DC
Contributor(s):Michael L. Klein
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/08/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/08/30
Tag:NADH:ubiquinone oxidoreductase; cell respiration; diffusion model; electron transfer; molecular simulations
Issue:Art. 201805468
Page Number:8
First Page:1
Last Page:8
This open access article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).
Institutes:Physik / Physik
Angeschlossene und kooperierende Institutionen / MPI für Biophysik
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0