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Redox-induced activation of the proton pump in the respiratory complex I

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Redox-induced activation of the proton pump in the respiratory complex I. / Sharma, Vivek; Belevich, Galina; Gamiz-Hernandez, Ana P.; Róg, Tomasz; Vattulainen, Ilpo; Verkhovskaya, Marina L.; Wikström, Mårten; Hummer, Gerhard; Kaila, Ville R I.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 37, 15.09.2015, p. 11571-11576.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Sharma, V, Belevich, G, Gamiz-Hernandez, AP, Róg, T, Vattulainen, I, Verkhovskaya, ML, Wikström, M, Hummer, G & Kaila, VRI 2015, 'Redox-induced activation of the proton pump in the respiratory complex I', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 37, pp. 11571-11576. https://doi.org/10.1073/pnas.1503761112

APA

Sharma, V., Belevich, G., Gamiz-Hernandez, A. P., Róg, T., Vattulainen, I., Verkhovskaya, M. L., ... Kaila, V. R. I. (2015). Redox-induced activation of the proton pump in the respiratory complex I. Proceedings of the National Academy of Sciences of the United States of America, 112(37), 11571-11576. https://doi.org/10.1073/pnas.1503761112

Vancouver

Sharma V, Belevich G, Gamiz-Hernandez AP, Róg T, Vattulainen I, Verkhovskaya ML et al. Redox-induced activation of the proton pump in the respiratory complex I. Proceedings of the National Academy of Sciences of the United States of America. 2015 Sep 15;112(37):11571-11576. https://doi.org/10.1073/pnas.1503761112

Author

Sharma, Vivek ; Belevich, Galina ; Gamiz-Hernandez, Ana P. ; Róg, Tomasz ; Vattulainen, Ilpo ; Verkhovskaya, Marina L. ; Wikström, Mårten ; Hummer, Gerhard ; Kaila, Ville R I. / Redox-induced activation of the proton pump in the respiratory complex I. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 37. pp. 11571-11576.

Bibtex - Download

@article{902de957bf7b4f23966bd6967adfd338,
title = "Redox-induced activation of the proton pump in the respiratory complex I",
abstract = "Complex I functions as a redox-linked proton pump in the respiratory chains of mitochondria and bacteria, driven by the reduction of quinone (Q) by NADH. Remarkably, the distance between the Q reduction site and the most distant proton channels extends nearly 200 {\AA}. To elucidate the molecular origin of this long-range coupling, we apply a combination of large-scale molecular simulations and a site-directed mutagenesis experiment of a key residue. In hybrid quantum mechanics/molecular mechanics simulations, we observe that reduction of Q is coupled to its local protonation by the His-38/Asp-139 ion pair and Tyr-87 of subunit Nqo4. Atomistic classical molecular dynamics simulations further suggest that formation of quinol (QH2) triggers rapid dissociation of the anionic Asp-139 toward the membrane domain that couples to conformational changes in a network of conserved charged residues. Site-directed mutagenesis data confirm the importance of Asp-139; upon mutation to asparagine the Q reductase activity is inhibited by 75{\%}. The current results, together with earlier biochemical data, suggest that the proton pumping in complex I is activated by a unique combination of electrostatic and conformational transitions.",
keywords = "Cell respiration, Electron transfer, Molecular dynamics simulations, NADH-quinone oxidoreductase, QM/MM simulations",
author = "Vivek Sharma and Galina Belevich and Gamiz-Hernandez, {Ana P.} and Tomasz R{\'o}g and Ilpo Vattulainen and Verkhovskaya, {Marina L.} and M{\aa}rten Wikstr{\"o}m and Gerhard Hummer and Kaila, {Ville R I}",
year = "2015",
month = "9",
day = "15",
doi = "10.1073/pnas.1503761112",
language = "English",
volume = "112",
pages = "11571--11576",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "37",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Redox-induced activation of the proton pump in the respiratory complex I

AU - Sharma, Vivek

AU - Belevich, Galina

AU - Gamiz-Hernandez, Ana P.

AU - Róg, Tomasz

AU - Vattulainen, Ilpo

AU - Verkhovskaya, Marina L.

AU - Wikström, Mårten

AU - Hummer, Gerhard

AU - Kaila, Ville R I

PY - 2015/9/15

Y1 - 2015/9/15

N2 - Complex I functions as a redox-linked proton pump in the respiratory chains of mitochondria and bacteria, driven by the reduction of quinone (Q) by NADH. Remarkably, the distance between the Q reduction site and the most distant proton channels extends nearly 200 Å. To elucidate the molecular origin of this long-range coupling, we apply a combination of large-scale molecular simulations and a site-directed mutagenesis experiment of a key residue. In hybrid quantum mechanics/molecular mechanics simulations, we observe that reduction of Q is coupled to its local protonation by the His-38/Asp-139 ion pair and Tyr-87 of subunit Nqo4. Atomistic classical molecular dynamics simulations further suggest that formation of quinol (QH2) triggers rapid dissociation of the anionic Asp-139 toward the membrane domain that couples to conformational changes in a network of conserved charged residues. Site-directed mutagenesis data confirm the importance of Asp-139; upon mutation to asparagine the Q reductase activity is inhibited by 75%. The current results, together with earlier biochemical data, suggest that the proton pumping in complex I is activated by a unique combination of electrostatic and conformational transitions.

AB - Complex I functions as a redox-linked proton pump in the respiratory chains of mitochondria and bacteria, driven by the reduction of quinone (Q) by NADH. Remarkably, the distance between the Q reduction site and the most distant proton channels extends nearly 200 Å. To elucidate the molecular origin of this long-range coupling, we apply a combination of large-scale molecular simulations and a site-directed mutagenesis experiment of a key residue. In hybrid quantum mechanics/molecular mechanics simulations, we observe that reduction of Q is coupled to its local protonation by the His-38/Asp-139 ion pair and Tyr-87 of subunit Nqo4. Atomistic classical molecular dynamics simulations further suggest that formation of quinol (QH2) triggers rapid dissociation of the anionic Asp-139 toward the membrane domain that couples to conformational changes in a network of conserved charged residues. Site-directed mutagenesis data confirm the importance of Asp-139; upon mutation to asparagine the Q reductase activity is inhibited by 75%. The current results, together with earlier biochemical data, suggest that the proton pumping in complex I is activated by a unique combination of electrostatic and conformational transitions.

KW - Cell respiration

KW - Electron transfer

KW - Molecular dynamics simulations

KW - NADH-quinone oxidoreductase

KW - QM/MM simulations

UR - http://www.scopus.com/inward/record.url?scp=84941671298&partnerID=8YFLogxK

U2 - 10.1073/pnas.1503761112

DO - 10.1073/pnas.1503761112

M3 - Article

VL - 112

SP - 11571

EP - 11576

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 37

ER -