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At the heart of their energy metabolism lies the Hdr\u2013Vhu\u2013Fwd super-assembly, which couples H\n                    <jats:sub>2<\/jats:sub>\n                    oxidation with CO\n                    <jats:sub>2<\/jats:sub>\n                    reduction through flavin-based electron bifurcation. Here we present the cryogenic electron microscopy structure of the Hdr\u2013Vhu\u2013Fwd super-assembly from\n                    <jats:italic>Methanococcus maripaludis<\/jats:italic>\n                    , revealing an 8\u2009MDa complex comprising 252 polypeptide chains and over 600 redox cofactors. Cryo-electron tomography further support that this super-assembly forms an intact structure within the cytoplasm of intact cells. This architecture comprises two hexameric HdrABC\u2013Vhu rings linked by a tetrameric FwdF core, forming a continuous, circular electron chain. In this unique arrangement, 12 polyferredoxin subunits (VhuB) connect the Vhu\u2013Hdr and Fwd complexes, thereby coupling electron bifurcation with CO\n                    <jats:sub>2<\/jats:sub>\n                    reduction and directly linking the last and the first step of methanogenesis. Moreover, we identify a modular variant of the complex in which the [NiFe]-hydrogenase Vhu is substituted by tungsten-containing formate dehydrogenase (FdhAB), indicating flexible integration of electron-input modules facilitating metabolic adaptation under diverse environmental conditions\n                    <jats:sup>2<\/jats:sup>\n                    . Analysis of the taxonomic distribution reveals that this architecture is specific to class I methanogens and is distinct from the smaller Hdr\u2013Fmd complex of class II\n                    <jats:sup>3<\/jats:sup>\n                    . Together, our study reveals that the the Hdr\u2013Vhu\u2013Fwd super-assembly has a modular and adaptable bioenergetic assembly, suggesting a lineage-specific architecture to adapt to diverse anaerobic niches.\n                  <\/jats:p>","DOI":"10.1038\/s41586-026-10744-9","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:02:52Z","timestamp":1783522972000},"page":"1054-1063","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Architecture of the 8 MDa Hdr\u2013Vhu\u2013Fwd super-assembly in class I methanogens"],"prefix":"10.1038","volume":"656","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7753-7337","authenticated-orcid":false,"given":"Sophia","family":"Paul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas C.","family":"Pascoa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7211-7029","authenticated-orcid":false,"given":"Max A.","family":"Klamke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9196-622X","authenticated-orcid":false,"given":"Stefan","family":"Bohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0320-2690","authenticated-orcid":false,"given":"Frank","family":"Abendroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0882-5499","authenticated-orcid":false,"given":"Darja","family":"Deobald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7555-1865","authenticated-orcid":false,"given":"Olalla","family":"V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-0258","authenticated-orcid":false,"given":"Sven T.","family":"Stripp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9121-1764","authenticated-orcid":false,"given":"Jan M.","family":"Schuller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"10744_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.111504","volume":"27","author":"Y Ding","year":"2024","unstructured":"Ding, Y. et al. 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