A Bacillales-specific tubular scaffold essential for NADH dehydrogenase activity
Abstract Respiratory type II NADH:quinone oxidoreductases (NDH-II) are typically monotopic flavoproteins that make direct contact with the membrane to access the quinone pool. Here, we show that in Bacillus subtilis , one NDH-II, termed Ndh, assembles with the helical membrane plugin (HMP) protein YjlC and forms supramolecular fibers. Genetic and biochemical analyses demonstrate that Ndh and YjlC proteins are essential for NADH oxidation. Cryo-EM analysis reveals that YjlC forms a tubular scaffold onto which multiple Ndh subunits are regularly docked via their C-terminal domain, repurposed from its classical role in direct membrane binding. These fibers can extend up to ~1000 Å, creating a continuous hydrophobic tunnel filled with lipids and quinones, thereby mimicking the membrane environment. Comparative genomics unveils that this partnership arose exclusively within Bacillales through the recruitment of an ancestral HMP originally associated with sulfide:quinone reductases. Together, our findings uncover a lineage-specific structural adaptation in which NDH-II enzymes depend on an HMP scaffold, expanding their functional diversity beyond the classical monotopic paradigm.
Authors
- Anne Walburger (ORCID: https://orcid.org/0000-0003-1204-1523)
- Pierre Garcia (ORCID: https://orcid.org/0000-0001-7444-899X)
- Cyrille Y. Botté (ORCID: https://orcid.org/0000-0002-2245-536X)
- Yvain Nicolet (ORCID: https://orcid.org/0000-0002-4189-7067)
- Pauline Juyoux (ORCID: https://orcid.org/0000-0003-3153-1376)
- Mickaël V. Cherrier (ORCID: https://orcid.org/0000-0003-0724-6663)
- Guy Schoehn (ORCID: https://orcid.org/0000-0002-1459-3201)
- Fabien Pierrel (ORCID: https://orcid.org/0000-0003-2083-3002)
- Maria J. Mate
- Salomé Sauvage (ORCID: https://orcid.org/0000-0002-2277-3798)
- Axel Magalon (ORCID: https://orcid.org/0000-0002-3375-738X)
- Yoshiki Yamaryo‐Botté (ORCID: https://orcid.org/0000-0002-9349-4411)
- Artémis Kosta (ORCID: https://orcid.org/0000-0001-7115-4566)
- Régine Lebrun (ORCID: https://orcid.org/0000-0002-1491-9013)
- Farida Seduk
- R Osman (ORCID: https://orcid.org/0000-0003-2803-8783)
- Lilou Bizien-Jaglin
Institutions
- Institut polytechnique de Grenoble (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Aix-Marseille Université (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- CEA Grenoble (FR)
- Institut des Matériaux, de Microélectronique et des Nanosciences de Provence (FR)
- Institut de Biologie Structurale (FR)
- Université Grenoble Alpes (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-06-18
- DOI
- https://doi.org/10.1038/s41467-026-74385-2
- Primary Topic
- Photosynthetic Processes and Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00