Bibliographic Details
| Title: |
Structural and mechanistic basis of the central energy-converting methyltransferase complex of methanogenesis. |
| Authors: |
Aziz, Iram1, Kayastha, Kanwal1, Kaltwasser, Susann2, Vonck, Janet3, Welsch, Sonja2, Murphy, Bonnie J.4, Kahnt, Jörg5, Di Wu1, Wagner, Tristan6, Shima, Seigo5, Ermler, Ulrich1 ulrich.ermler@biophys.mpg.de |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America. 4/2/2024, Vol. 121 Issue 14, p1-10. 34p. |
| Subject Terms: |
*METHYLTRANSFERASES, *VITAMIN B12, *FOLIC acid, *MEMBRANE proteins, *BIOGEOCHEMICAL cycles, *PERMEATION tubes, *ARAMID fibers |
| 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. [ABSTRACT FROM AUTHOR] |
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