德国马尔堡大学Jan Michael Schuller研究组近日取得一项新成果。经过不懈努力，他们研制了ATP驱动的甲基辅酶M还原酶激活复合物的结构。相关论文于2025年4月16日发表在《自然》杂志上。

本研究纯化了马里帕鲁氏甲烷球菌的MCR活化复合物，并对其进行了表征。McrC是MCR操纵子中编码的一个小亚基，与产甲烷标记蛋白Mmp7、Mmp17、Mmp3和A2组分共同纯化。研究组证明了这种复合物可以在体外以严格依赖atp的方式激活MCR，使甲烷的形成成为可能。此外，该课题组确定了MCR活化复合物的低温电镜结构，具有不同的功能状态，局部分辨率达到1.8-2.1。他们的数据显示，三种复杂的铁硫离子形成了通往F430的电子转移途径。拓扑分析和电子顺磁共振谱分析表明，这些色谱仪与[8Fe-9S-C]色谱仪相似，后者是氮酶催化辅助因子的成熟中间体。总之，他们的发现为MCR的激活机制提供了新的见解，并对氮酶的早期进化进行了展望。

据悉，甲基辅酶M还原酶（MCR）是几乎所有生物生成甲烷的酶。其活性位点包括辅酶F₄₃₀，这是一种以卟啉为基础的辅助因子，中心有镍离子，仅在Ni(I)态下活性。产甲烷古菌是如何进行F₄₃₀的还原激活的，这代表了他们对自然界最古老的生物能量系统之一的理解的一个主要差距。

附：英文原文

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

Author: Ramrez-Amador, Fidel, Paul, Sophia, Kumar, Anuj, Lorent, Christian, Keller, Sebastian, Bohn, Stefan, Nguyen, Thinh, Lometto, Stefano, Vlegels, Dennis, Kahnt, Jrg, Deobald, Darja, Abendroth, Frank, Vzquez, Olalla, Hochberg, Georg, Scheller, Silvan, Stripp, Sven T., Schuller, Jan Michael

Issue&Volume: 2025-04-16

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. 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.

DOI: 10.1038/s41586-025-08890-7

Source: https://www.nature.com/articles/s41586-025-08890-7