mcrA encodes the alpha subunit of methyl-coenzyme M reductase (MCR), the key enzyme catalyzing the final step of methanogenesis in archaea. This enzyme converts methyl-coenzyme M and coenzyme B into methane and a heterodisulfide. The protein forms part of a hexameric complex containing two alpha, two beta, and two gamma chains. It contains a unique nickel-containing prosthetic group (coenzyme F430) essential for catalysis. In methanotrophic archaea, this enzyme can function in reverse for anaerobic methane oxidation. The gene serves as a molecular marker for detecting methanogens and methanotrophs in environmental samples.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Correct localization. MCR is a cytoplasmic enzyme complex as confirmed by UniProt curation. Supporting Evidence: file:METAC/mcrA/mcrA-falcon-research.md See deep research file for comprehensive analysis |
| GO:0015948 methanogenesis | IEA GO_REF:0000120 | ACCEPT | Summary: Core function annotation. McrA is essential for the final step of methanogenesis, converting methyl-coenzyme M to methane. This is the primary biological process for this gene. Supporting Evidence: PMID:11932238 The genome of M. acetivorans reveals extensive metabolic and physiological diversity PMID:37307484 Each active site contains F430, a unique Ni porphinoid that catalyzes the reduction of methyl-coenzyme M (CH3-CoM) by coenzyme B (CoB), yielding methane and a heterodisulfide |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | REMOVE | Summary: Too general. The specific molecular function is coenzyme-B sulfoethylthiotransferase activity (GO:0050524), which is already annotated. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MODIFY | Summary: Accurate but could be more specific. The protein binds nickel via coenzyme F430, a nickel-containing tetrapyrrole cofactor. Consider using nickel cation binding (GO:0016151) for specificity. Proposed replacements: nickel cation binding Supporting Evidence: PMID:37307484 Each active site contains F430, a unique Ni porphinoid that catalyzes the reduction of methyl-coenzyme M (CH3-CoM) by coenzyme B (CoB) |
| GO:0050524 coenzyme-B sulfoethylthiotransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core molecular function. This is the specific catalytic activity of methyl-coenzyme M reductase (EC 2.8.4.1), accurately representing the enzyme function. Supporting Evidence: PMID:29743535 Identification of a unique Radical SAM methyltransferase required for the sp(3)-C-methylation of an arginine residue of methyl-coenzyme M reductase PMID:37307484 Each active site contains F430, a unique Ni porphinoid that catalyzes the reduction of methyl-coenzyme M (CH3-CoM) by coenzyme B (CoB), yielding methane and a heterodisulfide |
| GO:0051291 protein heterooligomerization | IPI PMID:37307484 McrD binds asymmetrically to methyl-coenzyme M reductase imp... | NEW | Summary: McrA assembles with the beta and gamma subunits into the alpha2beta2gamma2 MCR heterohexamer, demonstrated by cryo-EM (PDB 8GF5/8GF6). Replaces the previous GO:0046983 "protein dimerization activity", which was incorrect for this hetero-oligomeric (not dimeric) assembly. Reason: Corrects the inaccurate GO:0046983 protein dimerization activity (MCR is a heterohexamer, not a dimer). Complex membership is captured separately by GO:0044674; this term captures the heterooligomerization property. Supporting Evidence: PMID:37307484 MCR is a C2-symmetric heterohexamer defined by Ξ±2Ξ²2Ξ³2 subunit stoichiometry |
| GO:0044674 methyl coenzyme M reductase complex | IPI PMID:37307484 McrD binds asymmetrically to methyl-coenzyme M reductase imp... | NEW | Summary: New cellular-component annotation. The cryo-EM structures of MCR from M. acetivorans (PDB 8GF5/8GF6) experimentally establish that McrA assembles into the alpha2beta2gamma2 methyl-coenzyme M reductase holoenzyme, in which McrA is the F430-bearing catalytic alpha subunit. No methyl coenzyme M reductase complex annotation existed previously. Reason: MCR holoenzyme complex term not present in existing_annotations; pinned by the cryo-EM structure of the assembled complex. Supporting Evidence: PMID:37307484 MCR is a C2-symmetric heterohexamer defined by Ξ±2Ξ²2Ξ³2 subunit stoichiometry PMID:37307484 two active sites formed at the interface of the Ξ±, Ξ±β², Ξ², and Ξ³ subunits |
| GO:0016151 nickel cation binding | IDA PMID:37307484 McrD binds asymmetrically to methyl-coenzyme M reductase imp... | NEW | Summary: New molecular-function annotation. The cryo-EM structure resolves the nickel tetrapyrrole cofactor coenzyme F430 bound in the McrA active site, with GlnΞ±161 identified as the F430 axial ligand, directly demonstrating nickel-cofactor binding by this protein. (GO:0046872 metal ion binding is also proposed for MODIFY to this same term.) Reason: Specific nickel cation binding (via coenzyme F430) is directly visualized in the structure; previously only the general GO:0046872 metal ion binding IEA existed. Supporting Evidence: PMID:37307484 Each active site contains F430, a unique Ni porphinoid that catalyzes the reduction of methyl-coenzyme M (CH3-CoM) by coenzyme B (CoB) PMID:37307484 containing the F430 axial ligand GlnΞ±161 |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: How do you distinguish mcrA sequences from methanogens versus methanotrophs using sequence features alone?
Suggested experts: Environmental microbiologists studying methane cycling, Phylogenetic analysis experts
Q: What sequence or structural features determine whether MCR operates in methanogenesis versus methanotrophy direction?
Suggested experts: Structural biologists, Archaeal metabolism experts
Experiment: Systematic comparison of mcrA sequences from known methanogens versus ANME archaea to identify discriminating features
Hypothesis: mcrA sequences from methanotrophs have distinct sequence signatures compared to methanogens
Type: Comparative genomics
Experiment: In vitro reconstitution experiments testing MCR activity under different redox conditions and with various electron donor/acceptor systems
Hypothesis: Thermodynamic conditions and partner proteins determine MCR directionality
Type: Biochemical characterization
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)