English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Redox-coupled quinone dynamics in the respiratory complex I

MPS-Authors
/persons/resource/persons194640

Warnau,  Judith
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;
Department Chemie, Technische Universität München, Garching, Germany;

/persons/resource/persons15259

Hummer,  Gerhard       
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;
Institute of Biophysics, Goethe University Frankfurt, Frankfurt am Main, Germany;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Warnau, J., Sharma, V., Gamiz-Hernandez, A. P., Di Luca, A., Haapanen, O., Vattulainen, I., et al. (2018). Redox-coupled quinone dynamics in the respiratory complex I. Proceedings of the National Academy of Sciences of the United States of America, 115(36), E8413-E8420. doi:10.1073/pnas.1805468115.


Cite as: https://hdl.handle.net/21.11116/0000-0003-5C19-B
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.