MtrA of the sodium ion pumping methyltransferase binds cobalamin in a unique mode.
In the three domains of life, vitamin B12 (cobalamin) is primarily used in methyltransferase and isomerase reactions. The methyltransferase complex MtrA-H of methanogenic archaea has a key function in energy conservation by catalysing the methyl transfer from methyl-tetrahydromethanopterin to coenzyme M and its coupling with sodium-ion translocation. The cobalamin-binding subunit MtrA is not homologous to any known B12-binding proteins and is proposed as the motor of the sodium-ion pump. Here, we present crystal structures of the soluble domain of the membrane-associated MtrA from Methanocaldococcus jannaschii and the cytoplasmic MtrA homologue/cobalamin complex from Methanothermus fervidus. The MtrA fold corresponds to the Rossmann-type α/β fold, which is also found in many cobalamin-containing proteins. Surprisingly, the cobalamin-binding site of MtrA differed greatly from all the other cobalamin-binding sites. Nevertheless, the hydrogen-bond linkage at the lower axial-ligand site of cobalt was equivalently constructed to that found in other methyltransferases and mutases. A distinct polypeptide segment fixed through the hydrogen-bond linkage in the relaxed Co(III) state might be involved in propagating the energy released upon corrinoid demethylation to the sodium-translocation site by a conformational change.
Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Straße 10, 35043 Marburg, Germany.
Tristan
T
Wagner
Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, 60438 Frankfurt am Main, Germany.
Ulrich
U
Ermler
Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Straße 10, 35043 Marburg, Germany.|PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, 332-0012 Saitama, Japan.
Seigo
S
Shima
D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000378:metabolism*; D002384:Catalysis; D003001:Cloning, Molecular; D019295:Computational Biology; D004734:Energy Metabolism; D017013:Methanobacteriaceae / Q000378:metabolism*; D063747:Methanocaldococcus; D008780:Methyltransferases / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D015222:Sodium Channels / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism
D001426:Bacterial Proteins; C115341:MtrA protein, methanobacterium; D015222:Sodium Channels; D008780:Methyltransferases; D014805:Vitamin B 12