Warnau 2018 Proc Natl Acad Sci U S A
| Warnau J, Sharma V, Gamiz-Hernandez AP, Di Luca A, Haapanen O, Vattulainen I, Wikström M, Hummer G, Kaila VRI (2018) Redox-coupled quinone dynamics in the respiratory complex I. Proc Natl Acad Sci U S A 115:E8413-20. https://doi.org/10.1073/pnas.1805468115 |
Warnau J, Sharma Vivek, Gamiz-Hernandez AP, Di Luca A, Haapanen O, Vattulainen I, Wikstroem Marten KF, Hummer G, Kaila Ville RI (2018) Proc Natl Acad Sci U S A
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, 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.
• Bioblast editor: Gnaiger E
Labels:
Preparation: Enzyme
Enzyme: Complex I
