9SFI

Heterodisulfide reductase-Formylmethanofuran dehydrogenase super-assembly

Summary for 9SFI

• Entry DOI: 10.2210/pdb9sfi/pdb
• EMDB information: 54825
• Descriptor: CoB--CoM heterodisulfide reductase iron-sulfur subunit A, Tungsten-containing formylmethanofuran dehydrogenase 2 subunit C, Formylmethanofuran dehydrogenase subunit D, ... (22 entities in total)
• Functional Keywords: methanogenesis, super-assembly, flavin-based elctron bifurcation, heterodisulfide-reductase, polyferredoxin, formylmethanofuran dehydrogenase, electron transport
• Biological source: Methanococcus maripaludis; More
• Total number of polymer chains: 42
• Total formula weight: 1404229.70

Authors

Paul, S.,Schuller, J.M. (deposition date: 2025-08-19, release date: 2026-07-01, Last modification date: 2026-07-22)

Primary citation

Paul, S.,Pascoa, T.C.,Klamke, M.A.,Bohn, S.,Abendroth, F.,Deobald, D.,Vazquez, O.,Stripp, S.T.,Schuller, J.M.
Architecture of the 8 MDa Hdr-Vhu-Fwd super-assembly in class I methanogens.
Nature, 2026

PubMed Abstract: Methanogens are central to global carbon cycling and among the largest biological sources of methane, a potent greenhouse gas. At the heart of their energy metabolism lies the Hdr-Vhu-Fwd super-assembly, which couples H oxidation with CO reduction through flavin-based electron bifurcation. Here we present the cryogenic electron microscopy structure of the Hdr-Vhu-Fwd super-assembly from Methanococcus maripaludis, revealing an 8 MDa 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-Vhu rings linked by a tetrameric FwdF core, forming a continuous, circular electron chain. In this unique arrangement, 12 polyferredoxin subunits (VhuB) connect the Vhu-Hdr and Fwd complexes, thereby coupling electron bifurcation with CO 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. Analysis of the taxonomic distribution reveals that this architecture is specific to class I methanogens and is distinct from the smaller Hdr-Fmd complex of class II. Together, our study reveals that the the Hdr-Vhu-Fwd super-assembly has a modular and adaptable bioenergetic assembly, suggesting a lineage-specific architecture to adapt to diverse anaerobic niches.

PubMed: 42420451
DOI: 10.1038/s41586-026-10744-9

Experimental method

ELECTRON MICROSCOPY (4 Å)