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

• 成果类型: Article
• 署名作者: Ramirez-Amador, Fidel; Paul, Sophia; Kumar, Anuj; Lorent, Christian; Keller, Sebastian; Bohn, Stefan; Nguyen, Thinh; Lometto, Stefano; Vlegels, Dennis; Kahnt, Joerg; Deobald, Darja; Abendroth, Frank; Vazquez, Olalla; Hochberg, Georg; Scheller, Silvan; Stripp, Sven T.; Schuller, Jan Michael
• 署名单位: Philipps University Marburg; Philipps University Marburg; Technical University of Berlin; Aalto University; Philipps University Marburg; Max Planck Society; Philipps University Marburg; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); University of Potsdam
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2077
• DOI: 10.1038/s41586-025-08890-7
• 发表日期: 2025-06-19
• 关键词: thermoautotrophicum-delta-h; m methylreductase system; crystal-structure; nickel enzyme; key enzyme; oxidation; saturation; f430; biosynthesis; mechanism

摘要

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 & Aring;. 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.