{"gene":"PF3D7_1103400","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2017,"finding":"PfSufD (PF3D7_1103400) forms a complex with apicoplast-encoded PfSufB and apicoplast-targeted PfSufC, as demonstrated by in vitro interaction experiments and in vivo cross-linking. The PfSufB-C2-D complex functions as a scaffold to assemble [4Fe-4S] clusters in vitro, and PfSufD enhances PfSufC ATPase activity.","method":"In vitro interaction experiments, in vivo cross-linking, in vitro [4Fe-4S] cluster assembly assay, ATPase activity assay","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution of complex and cluster assembly, ATPase activity assay with multiple orthogonal methods in a single study","pmids":["28695709"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"SufD (PF3D7_1103400) is refractory to targeted gene deletion in Plasmodium berghei blood stages, indicating it is essential for asexual blood stage growth in vivo. Endogenous tagging with a fluorescent marker demonstrated that SufD localizes to the apicoplast.","method":"Targeted gene deletion attempt (P. berghei), fluorescent tagging of endogenous locus, fluorescence microscopy","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic essentiality confirmed by refractory gene deletion, apicoplast localization confirmed by endogenous fluorescent tagging, single lab but two orthogonal methods","pmids":["24586983"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"SufD (PF3D7_1103400) is essential for Plasmodium falciparum parasite survival; deletion using a chemical bypass method was lethal. Unlike deletion of the cysteine desulfurase SufS, deletion of SufD did not disrupt the apicoplast organelle or cause loss of the organellar genome, indicating SufD's essential role is specifically in iron-sulfur cluster assembly rather than organelle maintenance.","method":"Conditional gene deletion using chemical bypass, apicoplast organelle integrity assay, organellar genome retention assay","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with specific phenotypic readouts (organelle integrity, genome retention) distinguishing SufD's role from SufS, single lab but multiple orthogonal readouts","pmids":["37166116"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"SufD (PF3D7_1103400) is an apicoplast-localized iron-sulfur cluster assembly protein in Plasmodium that forms a PfSufB-C2-D scaffold complex required for [4Fe-4S] cluster assembly in vitro, enhances PfSufC ATPase activity, and is essential for parasite blood-stage survival—with its essentiality attributed specifically to its role in Fe-S cluster biogenesis rather than apicoplast organelle maintenance."},"narrative":{"mechanistic_narrative":"SufD (PF3D7_1103400) is an apicoplast-localized component of the Plasmodium SUF iron-sulfur cluster biogenesis pathway required for asexual blood-stage survival [PMID:28695709, PMID:24586983, PMID:37166116]. It assembles with apicoplast-encoded PfSufB and apicoplast-targeted PfSufC into a PfSufB-C2-D scaffold complex that reconstitutes [4Fe-4S] clusters in vitro, and within this complex SufD enhances the ATPase activity of PfSufC [PMID:28695709]. SufD is refractory to gene deletion in P. berghei blood stages and lethal upon conditional deletion in P. falciparum [PMID:24586983, PMID:37166116]; unlike deletion of the cysteine desulfurase SufS, loss of SufD leaves the apicoplast organelle and its genome intact, establishing that its essential function lies specifically in Fe-S cluster assembly rather than organelle maintenance [PMID:37166116]. Beyond its role in this scaffold complex and Fe-S cluster biogenesis, no further mechanistic detail about SufD has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing whether SufD is dispensable and where it acts localized the protein to the apicoplast and demonstrated it is required for blood-stage growth, setting up its candidacy as an essential metabolic factor.","evidence":"Targeted gene deletion attempt and endogenous fluorescent tagging with microscopy in P. berghei","pmids":["24586983"],"confidence":"High","gaps":["Deletion refractoriness alone does not distinguish essentiality from a technical failure to recover deletants","Does not identify SufD's molecular activity or binding partners","Localization shown in P. berghei only"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"claim":"Reconstituting the SufB-C2-D complex answered how SufD contributes biochemically, showing it is a scaffold subunit for [4Fe-4S] assembly and a positive regulator of PfSufC ATPase activity.","evidence":"In vitro interaction and in vivo cross-linking, in vitro [4Fe-4S] cluster assembly assay, and ATPase activity assay in P. falciparum","pmids":["28695709"],"confidence":"High","gaps":["Stoichiometry and structural basis of the SufB-C2-D scaffold not resolved","Mechanism by which SufD enhances PfSufC ATPase activity not defined","Downstream Fe-S recipient apoproteins not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Conditional deletion resolved whether SufD's essentiality reflects Fe-S biogenesis or organelle upkeep, showing loss is lethal without disrupting the apicoplast or its genome and thereby assigning its essential role specifically to cluster assembly.","evidence":"Conditional gene deletion by chemical bypass with apicoplast organelle integrity and organellar genome retention readouts in P. falciparum","pmids":["37166116"],"confidence":"High","gaps":["The essential Fe-S-dependent client pathway that makes SufD indispensable is not pinpointed","Does not establish in vivo the scaffold mechanism inferred from in vitro reconstitution"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The physiological Fe-S cluster recipient apoproteins that depend on SufD and the structural mechanism of the SufB-C2-D scaffold remain unknown.","evidence":"","pmids":[],"confidence":"High","gaps":["No identified downstream Fe-S client accounting for essentiality","No structural model of the SufB-C2-D complex","Mechanism of SufC ATPase stimulation by SufD undefined"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfSufB-C2-D scaffold complex"],"partners":["PFSUFB","PFSUFC"],"other_free_text":["Essential for asexual blood-stage growth in P. berghei (refractory to deletion) and lethal upon conditional deletion in P. falciparum","Essential role is specific to Fe-S cluster assembly, not apicoplast organelle or organellar genome maintenance, distinguishing it from the cysteine desulfurase SufS","Enhances PfSufC ATPase activity within the scaffold complex"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"28695709","id":"PMC_28695709","title":"[Fe-S] cluster assembly in the apicoplast and its indispensability in mosquito stages of the malaria parasite.","date":"2017","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/28695709","citation_count":30,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSufD"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24586983","id":"PMC_24586983","title":"Identification of vital and dispensable sulfur utilization factors in the Plasmodium apicoplast.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24586983","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37166116","id":"PMC_37166116","title":"The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron-sulfur cluster assembly and tRNA modification.","date":"2023","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/37166116","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4353,"output_tokens":964,"usd":0.013759,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5723,"output_tokens":1925,"usd":0.03837,"stage2_stop_reason":"end_turn"},"total_usd":0.052129,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"PfSufD (PF3D7_1103400) forms a complex with apicoplast-encoded PfSufB and apicoplast-targeted PfSufC, as demonstrated by in vitro interaction experiments and in vivo cross-linking. The PfSufB-C2-D complex functions as a scaffold to assemble [4Fe-4S] clusters in vitro, and PfSufD enhances PfSufC ATPase activity.\",\n      \"method\": \"In vitro interaction experiments, in vivo cross-linking, in vitro [4Fe-4S] cluster assembly assay, ATPase activity assay\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution of complex and cluster assembly, ATPase activity assay with multiple orthogonal methods in a single study\",\n      \"pmids\": [\"28695709\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"SufD (PF3D7_1103400) is refractory to targeted gene deletion in Plasmodium berghei blood stages, indicating it is essential for asexual blood stage growth in vivo. Endogenous tagging with a fluorescent marker demonstrated that SufD localizes to the apicoplast.\",\n      \"method\": \"Targeted gene deletion attempt (P. berghei), fluorescent tagging of endogenous locus, fluorescence microscopy\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic essentiality confirmed by refractory gene deletion, apicoplast localization confirmed by endogenous fluorescent tagging, single lab but two orthogonal methods\",\n      \"pmids\": [\"24586983\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SufD (PF3D7_1103400) is essential for Plasmodium falciparum parasite survival; deletion using a chemical bypass method was lethal. Unlike deletion of the cysteine desulfurase SufS, deletion of SufD did not disrupt the apicoplast organelle or cause loss of the organellar genome, indicating SufD's essential role is specifically in iron-sulfur cluster assembly rather than organelle maintenance.\",\n      \"method\": \"Conditional gene deletion using chemical bypass, apicoplast organelle integrity assay, organellar genome retention assay\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with specific phenotypic readouts (organelle integrity, genome retention) distinguishing SufD's role from SufS, single lab but multiple orthogonal readouts\",\n      \"pmids\": [\"37166116\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"SufD (PF3D7_1103400) is an apicoplast-localized iron-sulfur cluster assembly protein in Plasmodium that forms a PfSufB-C2-D scaffold complex required for [4Fe-4S] cluster assembly in vitro, enhances PfSufC ATPase activity, and is essential for parasite blood-stage survival—with its essentiality attributed specifically to its role in Fe-S cluster biogenesis rather than apicoplast organelle maintenance.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SufD (PF3D7_1103400) is an apicoplast-localized component of the Plasmodium SUF iron-sulfur cluster biogenesis pathway required for asexual blood-stage survival [#0, #1, #2]. It assembles with apicoplast-encoded PfSufB and apicoplast-targeted PfSufC into a PfSufB-C2-D scaffold complex that reconstitutes [4Fe-4S] clusters in vitro, and within this complex SufD enhances the ATPase activity of PfSufC [#0]. SufD is refractory to gene deletion in P. berghei blood stages and lethal upon conditional deletion in P. falciparum [#1, #2]; unlike deletion of the cysteine desulfurase SufS, loss of SufD leaves the apicoplast organelle and its genome intact, establishing that its essential function lies specifically in Fe-S cluster assembly rather than organelle maintenance [#2]. Beyond its role in this scaffold complex and Fe-S cluster biogenesis, no further mechanistic detail about SufD has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing whether SufD is dispensable and where it acts localized the protein to the apicoplast and demonstrated it is required for blood-stage growth, setting up its candidacy as an essential metabolic factor.\",\n      \"evidence\": \"Targeted gene deletion attempt and endogenous fluorescent tagging with microscopy in P. berghei\",\n      \"pmids\": [\"24586983\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Deletion refractoriness alone does not distinguish essentiality from a technical failure to recover deletants\",\n        \"Does not identify SufD's molecular activity or binding partners\",\n        \"Localization shown in P. berghei only\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Reconstituting the SufB-C2-D complex answered how SufD contributes biochemically, showing it is a scaffold subunit for [4Fe-4S] assembly and a positive regulator of PfSufC ATPase activity.\",\n      \"evidence\": \"In vitro interaction and in vivo cross-linking, in vitro [4Fe-4S] cluster assembly assay, and ATPase activity assay in P. falciparum\",\n      \"pmids\": [\"28695709\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Stoichiometry and structural basis of the SufB-C2-D scaffold not resolved\",\n        \"Mechanism by which SufD enhances PfSufC ATPase activity not defined\",\n        \"Downstream Fe-S recipient apoproteins not identified\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Conditional deletion resolved whether SufD's essentiality reflects Fe-S biogenesis or organelle upkeep, showing loss is lethal without disrupting the apicoplast or its genome and thereby assigning its essential role specifically to cluster assembly.\",\n      \"evidence\": \"Conditional gene deletion by chemical bypass with apicoplast organelle integrity and organellar genome retention readouts in P. falciparum\",\n      \"pmids\": [\"37166116\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The essential Fe-S-dependent client pathway that makes SufD indispensable is not pinpointed\",\n        \"Does not establish in vivo the scaffold mechanism inferred from in vitro reconstitution\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological Fe-S cluster recipient apoproteins that depend on SufD and the structural mechanism of the SufB-C2-D scaffold remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No identified downstream Fe-S client accounting for essentiality\",\n        \"No structural model of the SufB-C2-D complex\",\n        \"Mechanism of SufC ATPase stimulation by SufD undefined\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016226\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0051536\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016226\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\n      \"PfSufB-C2-D scaffold complex\"\n    ],\n    \"partners\": [\n      \"PfSufB\",\n      \"PfSufC\"\n    ],\n    \"other_free_text\": [\n      \"Essential for asexual blood-stage growth in P. berghei (refractory to deletion) and lethal upon conditional deletion in P. falciparum\",\n      \"Essential role is specific to Fe-S cluster assembly, not apicoplast organelle or organellar genome maintenance, distinguishing it from the cysteine desulfurase SufS\",\n      \"Enhances PfSufC ATPase activity within the scaffold complex\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1103400","name":null,"product":"iron-sulfur cluster assembly protein SufD","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0943500","name":null,"product":"iron-sulfur cluster assembly protein SufD","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0901000","name":null,"product":"iron-sulfur cluster assembly protein SufD, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SufD","evaluation":null}