Capturing a methanogenic carbon monoxide dehydrogenase/acetyl-CoA synthase complex via cryogenic electron microscopy

• 成果类型: Article
• 署名作者: Biester, Alison; Grahame, David A.; Drennan, Catherine L.
• 署名单位: Massachusetts Institute of Technology (MIT); Uniformed Services University of the Health Sciences - USA; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14382
• DOI: 10.1073/pnas.2410995121
• 发表日期: 2024-10-08
• 关键词: iron-sulfur protein; acetyl-coa; clostridium-thermoaceticum; methanosarcina-thermophila; rhodospirillum-rubrum; crystal-structure; enzyme complex; c-c; cluster; methylation

摘要

Approximately two- thirds of the estimated one- billion metric tons of methane produced annually by methanogens is derived from the cleavage of acetate. Acetate is broken down by a Ni- Fe- S- containing A- cluster within the enzyme acetyl-CoA synthase (ACS) to carbon monoxide (CO) and a methyl group (CH3+). The methyl group ultimately forms the greenhouse gas methane, whereas CO is converted to the greenhouse gas carbon dioxide (CO2) by a Ni- Fe- S- containing C- cluster within the enzyme carbon monoxide dehydrogenase (CODH). Although structures have been solved of CODH/ACS from acetogens, which use these enzymes to make acetate from CO2, no structure of a CODH/ACS from a methanogen has been reported. In this work, we use cryo- electron microscopy to reveal the structure of a methanogenic CODH and CODH/ACS from Methanosarcina thermophila (MetCODH/ACS). We find that the N- terminal domain of acetogenic ACS, which is missing in all methanogens, is replaced by a domain of CODH. This CODH domain provides a channel for CO to travel between the two catalytic Ni-Fe-S clusters. It generates the binding surface for ACS and creates a remarkably similar CO alcove above the A- cluster using residues from CODH rather than ACS. Comparison of our Met CODH/ACS structure with our Met CODH structure reveals a molecular mechanism to restrict gas flow from the CO channel when ACS departs, preventing CO escape into the cell. Overall, these long- awaited structures of a methanogenic CODH/ ACS reveal striking functional similarities to their acetogenic counterparts despite a substantial difference in domain organization.