Evidence map›Paper›PMID 26330610›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

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

Vivek Sharma, Galina Belevich, Ana P Gamiz-Hernandez, Tomasz Róg, Ilpo Vattulainen, Marina L Verkhovskaya, Mårten Wikström, Gerhard Hummer, Ville R I Kaila

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 130 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Hydration-Controlled Proton Transport in Respiratory Complex I.Journal of the American Chemical Society · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Binding of Natural Inhibitors to Respiratory Complex I.Pharmaceuticals (Basel, Switzerland) · 2022
    Review
  16. Respiratory complex I with charge symmetry in the membrane arm pumps protons.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  17. Review
  18. Article
  19. Article
  20. The coupling mechanism of mammalian mitochondrial complex I.Nature structural & molecular biology · 2022
    Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 3 countries.

Vivek SharmaDepartment of Physics, Tampere University of Technology, FI-33101 Tampere, Finland;
Galina BelevichHelsinki Bioenergetics Group, Programme for Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, FI-00014 Helsinki, Finland;
Ana P Gamiz-HernandezDepartment of Chemistry, Technische Universität München, D-85748 Garching, Germany;
Tomasz RógDepartment of Physics, Tampere University of Technology, FI-33101 Tampere, Finland;
Ilpo VattulainenDepartment of Physics, Tampere University of Technology, FI-33101 Tampere, Finland; MEMPHYS-Center for Biomembrane Physics, Department of Physics, University of Southern Denmark, DK-5230 Odense, Denmark;
Marina L VerkhovskayaHelsinki Bioenergetics Group, Programme for Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, FI-00014 Helsinki, Finland;
Mårten WikströmHelsinki Bioenergetics Group, Programme for Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, FI-00014 Helsinki, Finland;
Gerhard HummerDepartment of Theoretical Biophysics, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany.
Ville R I KailaDepartment of Chemistry, Technische Universität München, D-85748 Garching, Germany; ville.kaila@ch.tum.de.
University of Helsinki · FITampere University · FITechnical University of Munich · DEMax Planck Institute of Biophysics · DEUniversity of Southern Denmark · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 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.

Indexed as

Oxidation-ReductionElectron TransportElectron Transport Complex IEscherichia coliLipid BilayersMolecular Dynamics SimulationMutagenesis, Site-DirectedPhotosynthetic Reaction Center Complex ProteinsProtein BindingProtein Structure, TertiaryProton PumpsStatic ElectricityTemperatureThermus thermophilusX-RaysElectron Transport Complex ILipid BilayersPhotosynthetic Reaction Center Complex ProteinsProton Pumpscell respirationelectron transfermolecular dynamics simulationsNADH-quinone oxidoreductaseQM/MM simulations

Identifiers

PMID26330610
PMCPMC4577180
OpenAlexW2119707316

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.