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Molecular principles of redox-coupled sodium pumping of the ancient Rnf machinery
Open accessPreprint — published as 10.1038/s41467-025-57375-8 · Paper page
Abstract
The Rnf complex is the primary respiratory enzyme of several anaerobic prokaryotes that transfers electrons from ferredoxin to NAD + and pumps sodium ions (Na + ) across a membrane, powering ATP synthesis. Rnf is widespread in primordial organisms and the evolutionary predecessor of the Na + -pumping NADH-quinone oxidoreductase (Nqr) 1 . By running in reverse, Rnf reduces ferredoxin with NADH as reductant at the expense of the transmembrane electrochemical ion gradient and provides low potential electrons for nitrogenases as well as CO 2 reductases. Yet, the molecular principles that couple the long-range electron transfer to the Na + translocation across the membrane remain elusive. Here we resolve key functional states along the electron transfer pathway using redox-controlled cryo-electron microscopy (cryo-EM) that, in combination with biochemical functional assays and atomistic molecular simulations, provide key insight into the redox-driven Na + pumping mechanism. We show that the reduction of the unique membrane-embedded [2Fe2S] cluster in the vestibule between the RnfA/E subunits electrostatically attracts the sodium ions, and in turn, triggers an inward / outward transition with alternating membrane access driving the Na + pump and the reduction of NAD + . Our study unveils an ancient mechanism for redox-driven ion pumping, and provides key understanding of the fundamental principles governing energy conversion in biological systems.
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Metadata
- Authors
- Kumar, A., Roth, J., Kim, H., Saura, P., Bohn, S., Reif-Trauttmansdorff, T., Schubert, A., Kaila, V. R. I., Schuller, J. M., & Müller, V.
- Affiliations
- Goethe University Frankfurt (DE)
- Stockholm University (SE)
- Helmholtz Munich (DE)
- Philipps University of Marburg (DE)
- Corresponding author
- Kaila, Ville R. I.
- Schuller, Jan M.
- Müller, Volker
- ORCID
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2024-06-21
- Volume
- 16
- Issue
- 1
- Pages
- 2302-2302
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC11889175
- OpenAlex
- W4408167625
- Cited by
- 24
- References
- 1
- Citations by year
- 2026: 13 · 2025: 11
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Commission (101075992, HORIZON2020)
- Deutsche Forschungsgemeinschaft (SCHU 3364/1-1)
- Knut och Alice Wallenbergs Stiftelse (2019.0251)
- Vetenskapsrådet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Metalloenzymes and iron-sulfur proteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- Rnf complex, NADH:quinone oxidoreductase, nuclear quadrupole resonance, Acetobacterium woodii, ferredoxin, [2Fe-2S] cluster, long-range electron transfer, ion translocation, electrochemical gradient, nitrogenase, evolution of respiration, energy conversion
- MeSH terms
- Bacterial Proteins, Electron Transport, Ferredoxins, NAD, Oxidation-Reduction, Quinone Reductases, Sodium, Ion Transport, Cryoelectron Microscopy, Acetobacterium, Molecular Dynamics Simulation
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