9H1L

Methyl-coenzyme M reductase activation complex binding to the A2 component after incubation with ATP

Summary for 9H1L

• Entry DOI: 10.2210/pdb9h1l/pdb
• Related: 8S7V 8S7X
• EMDB information: 51767
• Descriptor: UPF0288 protein MmarC6_0796, FACTOR 430, 1-THIOETHANESULFONIC ACID, ... (17 entities in total)
• Functional Keywords: methyl-coenzyme m reductase, activation complex, atpase, iron-sulfur clusters, oxidoreductase
• Biological source: Methanococcus maripaludis; More
• Total number of polymer chains: 12
• Total formula weight: 489130.64

Authors

Ramirez-Amador, F.,Paul, S.,Kumar, A.,Schuller, J.M. (deposition date: 2024-10-09, release date: 2025-02-26, Last modification date: 2025-04-30)

Primary citation

Ramirez-Amador, F.,Paul, S.,Kumar, A.,Lorent, C.,Keller, S.,Bohn, S.,Nguyen, T.,Lometto, S.,Vlegels, D.,Kahnt, J.,Deobald, D.,Abendroth, F.,Vazquez, O.,Hochberg, G.,Scheller, S.,Stripp, S.T.,Schuller, J.M.
Structure of the ATP-driven methyl-coenzyme M reductase activation complex.
Nature, 2025

PubMed Abstract: Methyl-coenzyme M reductase (MCR) is the enzyme responsible for nearly all biologically generated methane. Its active site comprises coenzyme F, a porphyrin-based cofactor with a central nickel ion that is active exclusively in the Ni(I) state. How methanogenic archaea perform the reductive activation of F represents a major gap in our understanding of one of the most ancient bioenergetic systems in nature. Here we purified and characterized the MCR activation complex from Methanococcus maripaludis. McrC, a small subunit encoded in the mcr operon, co-purifies with the methanogenic marker proteins Mmp7, Mmp17, Mmp3 and the A2 component. We demonstrated that this complex can activate MCR in vitro in a strictly ATP-dependent manner, enabling the formation of methane. In addition, we determined the cryo-electron microscopy structure of the MCR activation complex exhibiting different functional states with local resolutions reaching 1.8-2.1 Å. Our data revealed three complex iron-sulfur clusters that formed an electron transfer pathway towards F. Topology and electron paramagnetic resonance spectroscopy analyses indicate that these clusters are similar to the [8Fe-9S-C] cluster, a maturation intermediate of the catalytic cofactor in nitrogenase. Altogether, our findings offer insights into the activation mechanism of MCR and prospects on the early evolution of nitrogenase.

PubMed: 40240609
DOI: 10.1038/s41586-025-08890-7

Experimental method

ELECTRON MICROSCOPY (2.14 Å)