Structural and mechanistic basis of the central energy-converting 
methyltransferase complex of methanogenesis

Aziz, Iram; Kayastha, Kanwal; Kaltwasser, Susann; Vonck, Janet; Welsch, Sonja; Murphy, Bonnie J.; Kahnt, Jörg; Wu, Di; Wagner, Tristan; Shima, Seigo; Ermler, Ulrich

doi:10.1073/pnas.2315568121

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Structural and mechanistic basis of the central energy-converting methyltransferase complex of methanogenesis

MPS-Authors

/persons/resource/persons254414

Kahnt, Jörg
Core Facility Mass Spectrometry and Proteomics, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons254714

Shima, Seigo
Department-Independent Research Group Microbial Protein Structure, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

External Resource

https://doi.org/10.1073/pnas.2315568121
(Publisher version)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Aziz, I., Kayastha, K., Kaltwasser, S., Vonck, J., Welsch, S., Murphy, B. J., et al. (2024). Structural and mechanistic basis of the central energy-converting methyltransferase complex of methanogenesis. Proceedings of the National Academy of Sciences of the United States of America, 121(14): e2315568121. doi:10.1073/pnas.2315568121.

Cite as: https://hdl.handle.net/21.11116/0000-000F-1828-A

Abstract

Methanogenic archaea inhabiting anaerobic environments play a crucial role in the global biogeochemical material cycle. The most universal electrogenic reaction of their methane-producing energy metabolism is catalyzed by N????5-methyl-tetrahydromethanopterin: coenzyme M methyltransferase (MtrABCDEFGH), which couples the vectorial Na+ transport with a methyl transfer between the one-carbon carriers tetrahydromethanopterin and coenzyme M via a vitamin B12 derivative (cobamide) as prosthetic group. We present the 2.08 Å cryo-EM structure of Mtr(ABCDEFG)3 composed of the central Mtr(ABFG)3 stalk symmetrically flanked by three membrane-spanning MtrCDE globes. Tetraether glycolipids visible in the map fill gaps inside the multisubunit complex. Putative coenzyme M and Na+ were identified inside or in a side-pocket of a cytoplasmic cavity formed within MtrCDE. Its bottom marks the gate of the transmembrane pore occluded in the cryo-EM map. By integrating Alphafold2 information, functionally competent MtrA?MtrH and MtrA?MtrCDE subcomplexes could be modeled and thus the methyl-tetrahydromethanopterin demethylation and coenzyme M methylation half-reactions structurally described. Methyl-transfer-driven Na+ transport is proposed to be based on a strong and weak complex between MtrCDE and MtrA carrying vitamin B12, the latter being placed at the entrance of the cytoplasmic MtrCDE cavity. Hypothetically, strongly attached methyl-cob(III)amide (His-on) carrying MtrA induces an inward-facing conformation, Na+ flux into the membrane protein center and finally coenzyme M methylation while the generated loosely attached (or detached) MtrA carrying cob(I)amide (His-off) induces an outward-facing conformation and an extracellular Na+ outflux. Methyl-cob(III)amide (His-on) is regenerated in the distant active site of the methyl-tetrahydromethanopterin binding MtrH implicating a large-scale shuttling movement of the vitamin B12-carrying domain.