McrD binds asymmetrically to methyl-coenzyme M reductase improving active-site accessibility during assembly

Area of Science:

• Biochemistry
• Microbiology
• Structural Biology

Background:

• Methyl-coenzyme M reductase (MCR) is crucial for biological methane production, catalyzing the final step in methanogenesis.
• MCR assembly involves complex posttranslational modifications and the insertion of the nickel-containing coenzyme F430.
• Despite its importance, the precise mechanisms of MCR assembly remain largely unknown.

Purpose of the Study:

• To elucidate the structural details of MCR assembly intermediates.
• To characterize the role of the novel protein McrD in the MCR assembly pathway.
• To provide insights into the insertion of coenzyme F430 into MCR.

Main Methods:

• X-ray crystallography was used to determine the structures of MCR in two intermediate assembly states.
• Biochemical analysis was performed to understand the interaction between MCR and McrD.
• Comparative structural analysis was employed to identify key conformational changes during assembly.

Main Results:

• Two novel MCR intermediate structures were resolved, lacking one or both coenzyme F430 molecules.
• The previously uncharacterized protein McrD was found to bind MCR asymmetrically.
• McrD binding was shown to displace MCR alpha subunits, increasing accessibility for coenzyme F430 installation.

Conclusions:

• The study reveals McrD as a key facilitator in MCR assembly, specifically aiding coenzyme F430 insertion.
• These findings offer critical insights for expressing MCR in heterologous systems.
• The identified structural mechanisms provide targets for developing MCR inhibitors, potentially impacting methane emissions.