The anaerobic cryo-EM structure of the methanogenic Mtr complex reveals a nitrogenase-like cluster bound to its active site

Authors

Reif-Trauttmansdorff, T., Kumar, A., Pascoa, T., Herderig, E., Bohn, S., Schmitz, R., Hochberg, G., Schuller, J.

Abstract

Methanogenic archaea conserve energy by coupling methyl-group transfer to the generation of a chemiosmotic sodium-ion (Na+) gradient. This central energy-conserving step is catalyzed by the membrane-bound N5-methyl-H4MPT:coenzyme M methyltransferase (Mtr). Here, we present high-resolution cryo-electron microscopy structures of the Mtr complex from Methanosarcina mazei determined under strictly anaerobic conditions. The structures reveal an unexpected, electron-dense metallocluster embedded within the central cavity of the MtrCDE trimer in the membrane plane. Based on the unique topology and density we modeled it as an [FeSC] L-type cluster. It is positioned adjacent to both the coenzyme M substrate and the corrinoid cofactor of MtrA in the MtrA-MtrCDE engaged state, thereby being located right at the catalytic core of the enzyme. We could further show that binding of MtrA to MtrCDE triggers rearrangements within the interface of MtrDE that widen a putative ion-conduction pathway. The proximity of the conserved sodium-binding site to the catalytic center suggests a putative link between methyl-transfer chemistry and Na+ translocation. In a broader context, these findings improve our understanding of how methyl transfer, analogous to redox chemistry, can drive chemiosmotic energy conversion.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 07 Jul 2026.

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