Redox-coupled quinone dynamics in the respiratory complex I.
Proc Natl Acad Sci U S A
; 115(36): E8413-E8420, 2018 09 04.
Article
em En
| MEDLINE
| ID: mdl-30120126
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Benzoquinonas
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Thermus thermophilus
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Yarrowia
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Complexo I de Transporte de Elétrons
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article