TY  - JOUR
A1  - Warnau, Judith
A1  - Sharma, Vivek
A1  - Gámiz-Hernández, Ana Patricia L
A1  - Di Luca, Andrea
A1  - Haapanen, Outi
A1  - Vattulainen, Ilpo
A1  - Wikström, Mårten
A1  - Hummer, Gerhard
A1  - Kaila, Ville R. I.
T1  - Redox-coupled quinone dynamics in the respiratory complex I
T2  - Proceedings of the National Academy of Sciences of the United States of America
N2  - 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.
KW  - NADH:ubiquinone oxidoreductase
KW  - diffusion model
KW  - electron transfer
KW  - molecular simulations
KW  - cell respiration
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46474
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-464748
SN  - 1091-6490
SN  - 0027-8424
N1  - This open access article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).
VL  - 115
IS  - Art. 201805468
SP  - 1
EP  - 8
PB  - National Acad. of Sciences
CY  - Washington, DC
ER  -