Structure of the ATP-driven methyl-coenzyme M reductase activation complex

Thumbnail Image

Files

Structure_of_the_ATP-driven_methyl-coenzyme_M_reductase_activation_complex.pdf (34.72 MB)

Access rights

openAccess
CC BY
publishedVersion

URL

Journal Title

Journal ISSN

Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
This publication is imported from Aalto University research portal.
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
Other link related to publication (opens in new window)
Unless otherwise stated, all rights belong to the author. You may download, display and print this publication for Your own personal use. Commercial use is prohibited.

Authors

Date

2025-06-19

Department

Department of Bioproducts and Biosystems

Major/Subject

Mcode

Degree programme

Language

en

Pages

8

Series

Nature, Volume 642, issue 8068, pp. 814-821

Abstract

Methyl-coenzyme M reductase (MCR) is the enzyme responsible for nearly all biologically generated methane1. Its active site comprises coenzyme F430, a porphyrin-based cofactor with a central nickel ion that is active exclusively in the Ni(I) state2,3. How methanogenic archaea perform the reductive activation of F430 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 F430. 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.

Description

Publisher Copyright: © The Author(s) 2025.

Keywords

Other note

DOI

10.1038/s41586-025-08890-7

Citation

Ramírez-Amador, F, Paul, S, Kumar, A, Lorent, C, Keller, S, Bohn, S, Nguyen, T, Lometto, S, Vlegels, D, Kahnt, J, Deobald, D, Abendroth, F, Vázquez, O, Hochberg, G, Scheller, S, Stripp, S T & Schuller, J M 2025, 'Structure of the ATP-driven methyl-coenzyme M reductase activation complex', Nature, vol. 642, no. 8068, 1091, pp. 814-821. https://doi.org/10.1038/s41586-025-08890-7

Permanent link to this item

https://urn.fi/URN:NBN:fi:aalto-202507045566

Collections

[article-cris] Kemian tekniikan korkeakoulu / CHEM