Last but not least, three iron-sulfur clusters shape an electron transfer pathway towards the exposed coenzyme F430. Unexpectedly, these clusters are reminiscent of the [8Fe-9S-C] cofactors (or L-clusters) that so far had only been found in the nitrogenase family.

But how is the catalytic pocket of MCR remodelled during activation? When complexed to the other components, the more 'proximal' half of MCR undergoes drastic conformational changes to expose the Ni-center in coenzyme F430, likely facilitating its further reduction.

To show the ATP-dependency activation of MCR, we followed the CH4 production at different scenarios (as isolated, ATP depletion, non-hydrolyzable ATP analogues). The external addition of ATP not only boosts the generation of CH4 but also promotes the interaction of A2 with MCR.

We used redox-controlled cryoEM to obtain different functional states (local resolutions as high as 1.8 angstrom!) of the activation complex asymetrically bound to MCR. The small McrC along with several methanogenic marker proteins (Mmp) and A2 (an ATPase) compose the complex.

I'm truly excited to announce our new publication in @nature.com unraveling a central picture of the Methyl-coenzyme M reductase (MCR) activation machinery and it's strong ATP dependency - kudos to @rnfr2d2.bsky.social for the fantastic illustration!

LINK: www.nature.com/articles/s41...