{
  "abstract": "Complex I is a large membrane protein that transduces redox energy into a proton motive force across a biological membrane, powering cellular respiration. Yet, despite significant experimental and computational efforts, its long-range proton translocation mechanism remains poorly understood. Here, we combine nuclear magnetic resonance spectroscopy and site-directed mutagenesis experiments with multiscale classical and hybrid quantum/classical (QM/MM) simulations to probe how conformational dynamics is linked to proton transfer reactions in the terminal antiporter module (Nqo12/NuoL/ND5) of Complex I. We show that protonation of a conserved proton-loading site (Lys329/His241Nqo12) in the terminal antiporter-like module gives rise to conformational changes that result in opening of the proton pathway. We further show that this protonation reaction is controlled by buried ion-pairs that modulate the barrier for proton translocation by intrinsic electric field effects. On a general level, our combined findings reveal how bioenergetic machines combine conformational dynamics with hydration transitions to establish efficient redox-driven proton pumps.",
  "abstract_shown": true,
  "affiliations": [
    "Stockholm University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "J. Liebau"
    },
    {
      "name": "P. Saura"
    },
    {
      "name": "S. Badolato"
    },
    {
      "name": "A. P. Gamiz-Hernandez"
    },
    {
      "affs": [
        0
      ],
      "name": "V. R. I. Kaila"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ch1728cmy9rmz.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.764137",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764137v1.full",
  "id": "ch1728cmy9rmz",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764137v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764137v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ch1728cmy9rmz.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T00:22:03Z",
      "native_id": "10.64898/2026.11.03.764137",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764137v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Electrostatic control of conformational dynamics drives proton translocation in respiratory Complex I",
  "title_text": "Electrostatic control of conformational dynamics drives proton translocation in respiratory Complex I",
  "type": "preprint",
  "updated_at": "2026-11-06T00:21:45Z",
  "url": "https://research.draconitic.com/paper/ch1728cmy9rmz",
  "venue": "bioRxiv",
  "versions": []
}