The small subunit of the corrinoid iron-sulfur protein (CFeSP), which acts as a methyl group carrier in the Wood-Ljungdahl pathway for CO2 fixation. AcsD binds a corrinoid (B12 derivative) cofactor and receives methyl groups from methyltetrahydrofolate methyltransferase (AcsE), subsequently transferring them to acetyl-CoA synthase (AcsB) for acetyl-CoA biosynthesis. Forms a heterohexamer complex with AcsC (large subunit) and AcsE.
The preferred accession for this review is Q07341. These relationships are manually assessed.
REFERENCE PROTEOME EQUIVALENT · Reviewed 2026-10-19
Reference proteome: UP000322283
Retain Q07341 as the primary Swiss-Prot accession. The reference corrinoid/iron-sulfur small-subunit sequence is exactly identical across all 323 residues. The changed organism code in the target entry name is not used as taxonomy evidence; live record/proteome taxon identifiers are checked. Retain the Swiss-Prot accession.
MMseqs2 searched 2,959 sequences across UP000322283 at E <= 1e-5 and sensitivity 7.5, returning 1 hits. Every returned sequence was globally aligned using BLOSUM62 with gap-open -10 and extension -0.5. Scores and sequences for all 1 returned candidates are retained, with 1 detailed alignment files. The heuristic search does not establish genomic absence or unique locus identity.
file:MOOTH/acsD/acsD-record-evidence.yaml
target_sequence_count: 2959
file:MOOTH/acsD/acsD-record-evidence.yaml
candidate_count: 1
A0A1D7XAJ1: 323 identities across 323 global-alignment columns (100.0% identity including gaps), 0 substitutions and 0 gap columns. Query coverage is 100.0%; target coverage is 100.0%. Sequence similarity is interpreted in the manual rationale. Identity over paired residues is 100.0000% (323/323); gap columns are excluded from this denominator.
file:MOOTH/acsD/acsD-record-evidence.yaml
query_length: 323 target_length: 323 alignment_columns: 323 identities: 323 mismatches: 0 gap_columns: 0 identity_percent: 100.0 query_coverage_percent: 100.0 target_coverage_percent: 100.0
The primary accession is outside every searched exact-taxon reference proteome. Current UniProt records place A0A1D7XAJ1 in UP000322283 and give it the same taxon as the primary.
file:MOOTH/acsD/acsD-record-evidence.yaml
primary_in_any_reference_proteome: false
file:MOOTH/acsD/acsD-record-evidence.yaml
alternative_in_reference_proteome: true
file:MOOTH/acsD/acsD-record-evidence.yaml
same_taxon: true
Sampled UniSave observations: 11-NOV-2015, entry version 76.: no Proteomes cross-reference; 12-AUG-2020, entry version 92.: no Proteomes cross-reference; 27-NOV-2024, entry version 105.: no Proteomes cross-reference. These dated observations do not establish uninterrupted membership/absence, the exact change date, or UniProt's motivation.
file:MOOTH/acsD/acsD-record-evidence.yaml
entry_date: 11-NOV-2015, entry version 76. proteomes: []
file:MOOTH/acsD/acsD-record-evidence.yaml
entry_date: 12-AUG-2020, entry version 92. proteomes: []
file:MOOTH/acsD/acsD-record-evidence.yaml
entry_date: 27-NOV-2024, entry version 105. proteomes: []
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006730 one-carbon metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: AcsD is directly involved in one-carbon metabolism through the Wood-Ljungdahl pathway, serving as a methyl group carrier that transfers C1 units from methyltetrahydrofolate to acetyl-CoA synthase. The crystal structure [PMID:22419154] and biochemical studies demonstrate its essential role in methyl transfer reactions using a corrinoid cofactor. Reason: This annotation accurately captures a core function of AcsD. The protein specifically handles one-carbon units (methyl groups) as part of the Wood-Ljungdahl pathway, transferring them from 5-methyl-H4folate to acetyl-CoA synthase via its corrinoid cofactor. This is well-supported by structural and biochemical evidence from PMID:22419154. Supporting Evidence: PMID:22419154 CFeSP then delivers the methyl group to the Ni2Fe4S4 active site metallocluster (A-cluster) of acetyl-CoA synthase (ACS), where it becomes the methyl of acetyl CoA PMID:22419154 For both MetH and CFeSP/MeTr, methyltetrahydrofolate (CH3-H4folate) is the methyl donor, and a protein-bound B12 derivative (cobalamin for MetH and 5′-methoxybenzimidazolyl cobamide for CFeSP) is the methyl carrier file:MOOTH/acsD/acsD-deep-research.md See deep research file for comprehensive analysis |
| GO:0015977 carbon fixation | IEA GO_REF:0000043 | MODIFY | Summary: AcsD is essential for carbon fixation via the Wood-Ljungdahl pathway, which fixes CO2 into acetyl-CoA. However, the more specific term GO:0030634 (carbon fixation by acetyl-CoA pathway) would better represent its precise function. Reason: While AcsD is indeed involved in carbon fixation, the generic term GO:0015977 is too broad. The protein specifically functions in the Wood-Ljungdahl (reductive acetyl-CoA) pathway, a specific type of carbon fixation. The more precise term GO:0030634 (carbon fixation by acetyl-CoA pathway) better captures this specificity. Proposed replacements: carbon fixation by acetyl-CoA pathway Supporting Evidence: PMID:22419154 Acetogenic bacteria, including M. thermoacetica, use CFeSP and MeTr together to catalyze methyltransfer in the Wood-Ljungdahl carbon fixation pathway for growth on CO2 as the sole carbon source |
| GO:0031419 cobalamin binding | IEA GO_REF:0000043 | ACCEPT | Summary: AcsD binds a corrinoid (B12 derivative) cofactor containing cobalt, which is essential for its methyl transfer function. Crystal structures [PMID:22419154] directly visualize the bound 5′-methoxybenzimidazolyl cobamide cofactor in the protein. Reason: This annotation is accurate and represents a core molecular function of AcsD. The protein contains a corrinoid-binding domain that specifically binds a B12 derivative (5′-methoxybenzimidazolyl cobamide in M. thermoacetica). This binding is essential for the methyl transfer activity and is directly observed in crystal structures. Supporting Evidence: PMID:22419154 a protein-bound B12 derivative (cobalamin for MetH and 5′-methoxybenzimidazolyl cobamide for CFeSP) is the methyl carrier PMID:22419154 electron density for the B12 cofactors is unambiguous (Supplementary Fig. 20), and density is also clear in several helical regions, including those near B12 |
| GO:0005515 protein binding | IPI PMID:22419154 Visualizing molecular juggling within a B12-dependent methyl... | MODIFY | Summary: While AcsD does interact with AcsC (forming heterohexamer) and AcsE (methyltransferase), the generic "protein binding" term is uninformative. More specific terms describing the functional complex formation would be more appropriate. Reason: The term "protein binding" is too vague and uninformative. AcsD forms specific functional complexes: it heterodimerizes with AcsC to form the corrinoid iron-sulfur protein, and this complex then associates with AcsE (methyltransferase) to form a ~220 kDa complex. A more specific term like "protein heterodimerization activity" (GO:0046982) or noting its participation in the "acetyl-CoA decarbonylase/synthase complex" (GO:0044672) would be more informative. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:22419154 Two CFeSPs are present in the complex, each containing two subunits PMID:22419154 In the ~220 kDa CFeSP/MeTr assembly (Fig. 1), the MeTr homodimer lies in the centre, with one CFeSP bound on either side |
| GO:0015977 carbon fixation | IDA PMID:22419154 Visualizing molecular juggling within a B12-dependent methyl... | MODIFY | Summary: Direct experimental evidence from PMID:22419154 demonstrates AcsD’s essential role in CO2 fixation via the Wood-Ljungdahl pathway. However, the more specific term GO:0030634 (carbon fixation by acetyl-CoA pathway) would better represent the specific pathway. Reason: While the IDA evidence strongly supports carbon fixation activity, the generic GO:0015977 term is too broad. The experimental evidence specifically demonstrates function in the Wood-Ljungdahl (reductive acetyl-CoA) pathway. GO:0030634 (carbon fixation by acetyl-CoA pathway) more accurately describes the specific type of carbon fixation demonstrated in the structural and biochemical studies. Proposed replacements: carbon fixation by acetyl-CoA pathway Supporting Evidence: PMID:22419154 Acetogenic bacteria, including M. thermoacetica, use CFeSP and MeTr together to catalyze methyltransfer in the Wood-Ljungdahl carbon fixation pathway for growth on CO2 as the sole carbon source PMID:22419154 Importantly, absorption features disappear when light is passed through the solution surrounding the crystals, indicating that spectra represent protein in crystals and not protein that may have been liberated into the solution. Collectively, these data demonstrate enzymatic transfer of the CH3-H4folate methyl group to CFeSP-bound B12 |
| GO:0005737 cytoplasm | IEA | NEW | Summary: AcsD functions in the cytoplasm as part of the Wood-Ljungdahl pathway for CO2 fixation in acetogenic bacteria. Reason: This cellular component term reflects AcsD's location where it operates as part of the cytoplasmic carbon fixation machinery. Supporting Evidence: PMID:22419154 Acetogenic bacteria, including M. thermoacetica, use CFeSP and MeTr together to catalyze methyltransfer in the Wood-Ljungdahl carbon fixation pathway for growth on CO2 as the sole carbon source |
| GO:0008168 methyltransferase activity | IEA | NEW | Summary: AcsD receives methyl groups from 5-methyltetrahydrofolate via its corrinoid cofactor and transfers them to acetyl-CoA synthase. Term updated from obsolete GO:0042084 to GO:0008168. Reason: AcsD's specific methyltransferase activity uses 5-methyltetrahydrofolate as the methyl donor via its bound corrinoid cofactor. Original term GO:0042084 was obsoleted as an unnecessary grouping term. Supporting Evidence: PMID:22419154 For both MetH and CFeSP/MeTr, methyltetrahydrofolate (CH3-H4folate) is the methyl donor, and a protein-bound B12 derivative (cobalamin for MetH and 5′-methoxybenzimidazolyl cobamide for CFeSP) is the methyl carrier PMID:22419154 CFeSP then delivers the methyl group to the Ni2Fe4S4 active site metallocluster (A-cluster) of acetyl-CoA synthase |
| GO:0044672 acetyl-CoA decarbonylase/synthase-carbon monoxide dehydrogenase complex | IEA | NEW | Summary: AcsD functions as part of the larger Wood-Ljungdahl pathway complex that includes acetyl-CoA synthase and other components. Reason: This cellular component term reflects AcsD's participation in the multi-enzyme complex responsible for CO2 fixation via the acetyl-CoA pathway. Supporting Evidence: PMID:22419154 In the ~220 kDa CFeSP/MeTr assembly (Fig. 1), the MeTr homodimer lies in the centre, with one CFeSP bound on either side. PMID:22419154 CFeSP then delivers the methyl group to the Ni2Fe4S4 active site metallocluster (A-cluster) of acetyl-CoA synthase (ACS), where it becomes the methyl of acetyl CoA |
| TEMP:CFeSP_complex corrinoid iron-sulfur protein heterodimer (with AcsC) | IEA | NEW | Summary: AcsD forms a heterodimeric corrinoid iron-sulfur protein (CFeSP) complex with AcsC, where AcsD serves as the small subunit. Reason: This cellular component term describes the specific heterodimeric complex that AcsD forms with AcsC, which is essential for its function in methyl transfer. Supporting Evidence: PMID:22419154 Two CFeSPs are present in the complex, each containing two subunits |
| GO:0030634 carbon fixation by acetyl-CoA pathway | IEA | NEW | Summary: AcsD is essential for carbon fixation via the Wood-Ljungdahl (reductive acetyl-CoA) pathway, which fixes CO2 into acetyl-CoA. Reason: This biological process term captures AcsD's specific role in the Wood-Ljungdahl pathway, a particular type of carbon fixation that was missing from existing annotations. Supporting Evidence: PMID:22419154 Acetogenic bacteria, including M. thermoacetica, use CFeSP and MeTr together to catalyze methyltransfer in the Wood-Ljungdahl carbon fixation pathway for growth on CO2 as the sole carbon source PMID:22419154 CFeSP then delivers the methyl group to the Ni2Fe4S4 active site metallocluster (A-cluster) of acetyl-CoA synthase (ACS), where it becomes the methyl of acetyl CoA |
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Download this section (compressed HTML)Q: How does AcsD coordinate methyl transfer between the corrinoid cofactor and the nickel center of acetyl-CoA synthase?
Q: What structural features of AcsD enable protection of the highly reactive methylcob(III)alamin intermediate from side reactions?
Q: How does the AcsD/AcsC complex regulate methyl transfer rates in response to cellular energy and carbon status?
Experiment: EPR and ENDOR spectroscopy to characterize transient radical intermediates during methyl transfer reactions
Experiment: Stopped-flow kinetics with fluorescent corrinoid analogs to measure methyl transfer rates between AcsD and partner proteins
Experiment: Hydrogen-deuterium exchange MS to map conformational changes in AcsD during the catalytic cycle
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