{"gene":"PF3D7_1413500","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2011,"finding":"Recombinant P. falciparum SufC (PF3D7_1413500) exhibits ATPase activity in vitro, and localizes to the apicoplast. SufC interacts with apicoplast-encoded SufB, demonstrated by in vitro interaction with an internal region of SufB and by co-elution of SufB from parasite lysate with recombinant SufC on an affinity column.","method":"Recombinant protein ATPase assay, apicoplast localization (implied by fractionation/import), affinity co-elution pulldown from parasite lysate","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ATPase activity demonstrated in vitro with recombinant protein; SufB–SufC interaction shown by two orthogonal methods (in vitro pulldown and affinity co-elution from parasite lysate), single lab","pmids":["21722645"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"Physical interaction between SufB (plastid-genome-encoded) and SufC (PF3D7_1413500, nucleus-encoded ATPase imported into the plastid) was demonstrated experimentally, providing early evidence for the SufBC complex in the malaria parasite apicoplast.","method":"Physical interaction assay (experimental evidence stated in abstract; specific method not fully described)","journal":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, interaction method not fully described in abstract, no mutagenesis or orthogonal confirmation reported here","pmids":["12594924"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Disruption of the Suf pathway in P. falciparum using a dominant negative mutant (targeting the pathway that includes SufC) results in loss of the apicoplast organelle and its genome, and parasites are only viable when supplemented with IPP, demonstrating that the Suf pathway (including SufC) is essential for apicoplast maintenance beyond its role in isoprenoid biosynthesis.","method":"Dominant negative mutant expression, chemical bypass with IPP, fluorescence microscopy for apicoplast maintenance, organellar genome PCR","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — dominant negative genetic disruption with IPP chemical bypass and organelle-loss phenotype, multiple readouts, single lab; SufC is a pathway component but the dominant negative targets the broader Suf pathway","pmids":["24086138"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"SufC (PF3D7_1413500) forms a complex with apicoplast-encoded SufB and apicoplast-targeted SufD, demonstrated by in vitro interaction experiments and in vivo cross-linking. The PfSufB-C2-D complex can assemble [4Fe-4S] clusters in vitro. ATPase activity of SufC is enhanced by SufD.","method":"In vitro protein interaction assays, in vivo chemical cross-linking, in vitro [4Fe-4S] cluster assembly assay, ATPase activity assay with SufD","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro FeS cluster assembly reconstitution combined with in vivo cross-linking and ATPase functional assay, multiple orthogonal methods in one study","pmids":["28695709"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"SUFC (PF3D7_1413500) in P. berghei is refractory to targeted gene deletion during asexual blood stages, demonstrating it is essential for blood-stage parasite survival in vivo. Endogenous tagging with a fluorescent marker confirmed that SufC localizes to the apicoplast.","method":"Targeted gene deletion attempts in P. berghei (experimental genetics), fluorescent tagging of endogenous locus, live imaging for localization","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic gene deletion (refractoriness as essentiality readout) combined with fluorescent tagging for localization, single lab, murine malaria model","pmids":["24586983"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"Deletion of SufC (PF3D7_1413500) using a chemical bypass method demonstrates it is essential for parasite survival in P. falciparum. Unlike deletion of SufS, deletion of SufC does not disrupt the apicoplast organelle or cause loss of the organellar genome, indicating SufC's essential role is specifically in FeS cluster assembly (scaffold/assembly steps) rather than in apicoplast organelle maintenance.","method":"Conditional gene deletion with IPP chemical bypass, fluorescence microscopy for apicoplast integrity, organellar genome PCR","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean conditional deletion with chemical bypass in P. falciparum, multiple orthogonal readouts (viability, organelle imaging, genome PCR), mechanistically distinguishes SufC from SufS, single lab but rigorous design","pmids":["37166116"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"SufC (PF3D7_1413500) is a nuclear-encoded ATPase that localizes to the P. falciparum apicoplast, where it forms a SufB–SufC2–SufD scaffold complex capable of assembling [4Fe-4S] clusters in vitro; SufD enhances its ATPase activity, it is essential for parasite survival in both P. falciparum and P. berghei, and its essentiality is attributable to its role in FeS cluster assembly rather than apicoplast organelle maintenance per se."},"narrative":{"mechanistic_narrative":"SufC (PF3D7_1413500) is a nuclear-encoded ATPase that is imported into the P. falciparum apicoplast, where it functions in the SUF pathway of [Fe-S] cluster biogenesis [PMID:21722645, PMID:24586983]. Recombinant SufC hydrolyzes ATP in vitro and interacts with the apicoplast-genome-encoded SufB through an internal region of SufB [PMID:21722645]. Together with apicoplast-targeted SufD, SufC assembles into a SufB–SufC2–SufD scaffold complex that reconstitutes [4Fe-4S] clusters in vitro, and SufD stimulates the ATPase activity of SufC [PMID:28695709]. SufC is essential for parasite survival in both P. berghei, where its gene is refractory to deletion in asexual blood stages [PMID:24586983], and P. falciparum, where conditional deletion is lethal unless rescued by IPP supplementation [PMID:37166116]. Unlike loss of SufS, SufC deletion does not cause loss of the apicoplast organelle or its genome, establishing that SufC's essential role lies specifically in the FeS cluster assembly steps rather than in organelle maintenance [PMID:37166116].","teleology":[{"year":2003,"claim":"Establishing whether the plastid-encoded SufB and the nucleus-encoded SufC physically associate was needed to define whether a SufBC assembly complex exists in the parasite apicoplast.","evidence":"Physical interaction assay between plastid-encoded SufB and imported SufC","pmids":["12594924"],"confidence":"Low","gaps":["Interaction method not fully described in the source","No mutagenesis or orthogonal confirmation reported","Functional consequence of the interaction not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Determining that SufC is an active ATPase localized to the apicoplast and binds a defined region of SufB provided the first biochemical characterization of SufC's enzymatic activity and its partner interface.","evidence":"Recombinant ATPase assay, apicoplast localization, and affinity co-elution of SufB from parasite lysate with recombinant SufC in P. falciparum","pmids":["21722645"],"confidence":"Medium","gaps":["ATPase activity shown only with recombinant protein, not in cellular context","Stoichiometry of the SufB–SufC complex not defined","Functional coupling of ATP hydrolysis to cluster assembly not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Perturbing the Suf pathway with a dominant negative mutant tested whether the pathway is essential beyond isoprenoid precursor supply and whether it maintains the apicoplast itself.","evidence":"Dominant negative mutant, IPP chemical bypass, apicoplast fluorescence microscopy, and organellar genome PCR in P. falciparum","pmids":["24086138"],"confidence":"Medium","gaps":["The dominant negative targets the broader Suf pathway rather than SufC specifically","Does not isolate SufC's individual contribution to the phenotype"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Testing whether SufC can be genetically deleted established that it is required for blood-stage parasite survival in a rodent malaria model and confirmed apicoplast localization in vivo.","evidence":"Targeted gene deletion refractoriness and endogenous fluorescent tagging with live imaging in P. berghei","pmids":["24586983"],"confidence":"Medium","gaps":["Refractoriness to deletion infers essentiality indirectly","Mechanism of essentiality not addressed","Restricted to asexual blood stages"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"claim":"Reconstituting the SufB–SufC2–SufD complex and showing it assembles [4Fe-4S] clusters in vitro defined the molecular scaffold in which SufC operates and revealed that SufD stimulates its ATPase activity.","evidence":"In vitro interaction assays, in vivo cross-linking, in vitro [4Fe-4S] cluster assembly, and ATPase assay with SufD in P. falciparum","pmids":["28695709"],"confidence":"High","gaps":["Structural basis of ATPase stimulation by SufD not resolved","Downstream recipients of assembled clusters not identified","How ATP hydrolysis is coupled to cluster transfer unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Conditional deletion of SufC with chemical bypass distinguished its essential role in FeS cluster assembly from organelle maintenance, showing that unlike SufS, SufC loss does not destroy the apicoplast or its genome.","evidence":"Conditional gene deletion with IPP chemical bypass, apicoplast fluorescence microscopy, and organellar genome PCR in P. falciparum","pmids":["37166116"],"confidence":"High","gaps":["The essential FeS-dependent downstream client(s) causing lethality not identified","Mechanistic reason for the divergent phenotype from SufS not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The essential downstream [Fe-S] cluster recipient proteins whose maturation depends on SufC, and the structural coupling between SufC ATP hydrolysis and cluster assembly/transfer, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No client apoprotein of the SufBC2D scaffold identified in the corpus","No structure of the P. falciparum SufBC2D complex","Mechanism linking ATPase cycle to cluster transfer unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["SufB–SufC2–SufD [4Fe-4S] cluster assembly scaffold complex","SufBC complex"],"partners":["SUFB (APICOPLAST-GENOME-ENCODED)","SUFD (APICOPLAST-TARGETED)"],"other_free_text":["Nuclear-encoded, imported into the apicoplast","Essential for asexual blood-stage survival in both P. falciparum and P. berghei","SufD stimulates SufC ATPase activity","Essentiality attributable to FeS cluster assembly, not apicoplast organelle/genome maintenance (contrasts with SufS)"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24086138","id":"PMC_24086138","title":"The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites.","date":"2013","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/24086138","citation_count":92,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21722645","id":"PMC_21722645","title":"Interaction between sulphur mobilisation proteins SufB and SufC: evidence for an iron-sulphur cluster biogenesis pathway in the apicoplast of Plasmodium falciparum.","date":"2011","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/21722645","citation_count":39,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SufC","PfSufC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":["PfSufC"],"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":["SufC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12594924","id":"PMC_12594924","title":"Parasite plastids: maintenance and functions.","date":"2003","source":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/12594924","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SufC"],"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":5673,"output_tokens":1803,"usd":0.022032,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6954,"output_tokens":2786,"usd":0.05221,"stage2_stop_reason":"end_turn"},"total_usd":0.074242,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"Recombinant P. falciparum SufC (PF3D7_1413500) exhibits ATPase activity in vitro, and localizes to the apicoplast. SufC interacts with apicoplast-encoded SufB, demonstrated by in vitro interaction with an internal region of SufB and by co-elution of SufB from parasite lysate with recombinant SufC on an affinity column.\",\n      \"method\": \"Recombinant protein ATPase assay, apicoplast localization (implied by fractionation/import), affinity co-elution pulldown from parasite lysate\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ATPase activity demonstrated in vitro with recombinant protein; SufB–SufC interaction shown by two orthogonal methods (in vitro pulldown and affinity co-elution from parasite lysate), single lab\",\n      \"pmids\": [\"21722645\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Physical interaction between SufB (plastid-genome-encoded) and SufC (PF3D7_1413500, nucleus-encoded ATPase imported into the plastid) was demonstrated experimentally, providing early evidence for the SufBC complex in the malaria parasite apicoplast.\",\n      \"method\": \"Physical interaction assay (experimental evidence stated in abstract; specific method not fully described)\",\n      \"journal\": \"Philosophical transactions of the Royal Society of London. Series B, Biological sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, interaction method not fully described in abstract, no mutagenesis or orthogonal confirmation reported here\",\n      \"pmids\": [\"12594924\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Disruption of the Suf pathway in P. falciparum using a dominant negative mutant (targeting the pathway that includes SufC) results in loss of the apicoplast organelle and its genome, and parasites are only viable when supplemented with IPP, demonstrating that the Suf pathway (including SufC) is essential for apicoplast maintenance beyond its role in isoprenoid biosynthesis.\",\n      \"method\": \"Dominant negative mutant expression, chemical bypass with IPP, fluorescence microscopy for apicoplast maintenance, organellar genome PCR\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — dominant negative genetic disruption with IPP chemical bypass and organelle-loss phenotype, multiple readouts, single lab; SufC is a pathway component but the dominant negative targets the broader Suf pathway\",\n      \"pmids\": [\"24086138\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"SufC (PF3D7_1413500) forms a complex with apicoplast-encoded SufB and apicoplast-targeted SufD, demonstrated by in vitro interaction experiments and in vivo cross-linking. The PfSufB-C2-D complex can assemble [4Fe-4S] clusters in vitro. ATPase activity of SufC is enhanced by SufD.\",\n      \"method\": \"In vitro protein interaction assays, in vivo chemical cross-linking, in vitro [4Fe-4S] cluster assembly assay, ATPase activity assay with SufD\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro FeS cluster assembly reconstitution combined with in vivo cross-linking and ATPase functional assay, multiple orthogonal methods in one study\",\n      \"pmids\": [\"28695709\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"SUFC (PF3D7_1413500) in P. berghei is refractory to targeted gene deletion during asexual blood stages, demonstrating it is essential for blood-stage parasite survival in vivo. Endogenous tagging with a fluorescent marker confirmed that SufC localizes to the apicoplast.\",\n      \"method\": \"Targeted gene deletion attempts in P. berghei (experimental genetics), fluorescent tagging of endogenous locus, live imaging for localization\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic gene deletion (refractoriness as essentiality readout) combined with fluorescent tagging for localization, single lab, murine malaria model\",\n      \"pmids\": [\"24586983\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Deletion of SufC (PF3D7_1413500) using a chemical bypass method demonstrates it is essential for parasite survival in P. falciparum. Unlike deletion of SufS, deletion of SufC does not disrupt the apicoplast organelle or cause loss of the organellar genome, indicating SufC's essential role is specifically in FeS cluster assembly (scaffold/assembly steps) rather than in apicoplast organelle maintenance.\",\n      \"method\": \"Conditional gene deletion with IPP chemical bypass, fluorescence microscopy for apicoplast integrity, organellar genome PCR\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean conditional deletion with chemical bypass in P. falciparum, multiple orthogonal readouts (viability, organelle imaging, genome PCR), mechanistically distinguishes SufC from SufS, single lab but rigorous design\",\n      \"pmids\": [\"37166116\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"SufC (PF3D7_1413500) is a nuclear-encoded ATPase that localizes to the P. falciparum apicoplast, where it forms a SufB–SufC2–SufD scaffold complex capable of assembling [4Fe-4S] clusters in vitro; SufD enhances its ATPase activity, it is essential for parasite survival in both P. falciparum and P. berghei, and its essentiality is attributable to its role in FeS cluster assembly rather than apicoplast organelle maintenance per se.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SufC (PF3D7_1413500) is a nuclear-encoded ATPase that is imported into the P. falciparum apicoplast, where it functions in the SUF pathway of [Fe-S] cluster biogenesis [#0, #4]. Recombinant SufC hydrolyzes ATP in vitro and interacts with the apicoplast-genome-encoded SufB through an internal region of SufB [#0]. Together with apicoplast-targeted SufD, SufC assembles into a SufB\\u2013SufC2\\u2013SufD scaffold complex that reconstitutes [4Fe-4S] clusters in vitro, and SufD stimulates the ATPase activity of SufC [#3]. SufC is essential for parasite survival in both P. berghei, where its gene is refractory to deletion in asexual blood stages [#4], and P. falciparum, where conditional deletion is lethal unless rescued by IPP supplementation [#5]. Unlike loss of SufS, SufC deletion does not cause loss of the apicoplast organelle or its genome, establishing that SufC's essential role lies specifically in the FeS cluster assembly steps rather than in organelle maintenance [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing whether the plastid-encoded SufB and the nucleus-encoded SufC physically associate was needed to define whether a SufBC assembly complex exists in the parasite apicoplast.\",\n      \"evidence\": \"Physical interaction assay between plastid-encoded SufB and imported SufC\",\n      \"pmids\": [\"12594924\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Interaction method not fully described in the source\", \"No mutagenesis or orthogonal confirmation reported\", \"Functional consequence of the interaction not addressed\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Determining that SufC is an active ATPase localized to the apicoplast and binds a defined region of SufB provided the first biochemical characterization of SufC's enzymatic activity and its partner interface.\",\n      \"evidence\": \"Recombinant ATPase assay, apicoplast localization, and affinity co-elution of SufB from parasite lysate with recombinant SufC in P. falciparum\",\n      \"pmids\": [\"21722645\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"ATPase activity shown only with recombinant protein, not in cellular context\", \"Stoichiometry of the SufB\\u2013SufC complex not defined\", \"Functional coupling of ATP hydrolysis to cluster assembly not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Perturbing the Suf pathway with a dominant negative mutant tested whether the pathway is essential beyond isoprenoid precursor supply and whether it maintains the apicoplast itself.\",\n      \"evidence\": \"Dominant negative mutant, IPP chemical bypass, apicoplast fluorescence microscopy, and organellar genome PCR in P. falciparum\",\n      \"pmids\": [\"24086138\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The dominant negative targets the broader Suf pathway rather than SufC specifically\", \"Does not isolate SufC's individual contribution to the phenotype\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Testing whether SufC can be genetically deleted established that it is required for blood-stage parasite survival in a rodent malaria model and confirmed apicoplast localization in vivo.\",\n      \"evidence\": \"Targeted gene deletion refractoriness and endogenous fluorescent tagging with live imaging in P. berghei\",\n      \"pmids\": [\"24586983\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Refractoriness to deletion infers essentiality indirectly\", \"Mechanism of essentiality not addressed\", \"Restricted to asexual blood stages\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Reconstituting the SufB\\u2013SufC2\\u2013SufD complex and showing it assembles [4Fe-4S] clusters in vitro defined the molecular scaffold in which SufC operates and revealed that SufD stimulates its ATPase activity.\",\n      \"evidence\": \"In vitro interaction assays, in vivo cross-linking, in vitro [4Fe-4S] cluster assembly, and ATPase assay with SufD in P. falciparum\",\n      \"pmids\": [\"28695709\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of ATPase stimulation by SufD not resolved\", \"Downstream recipients of assembled clusters not identified\", \"How ATP hydrolysis is coupled to cluster transfer unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Conditional deletion of SufC with chemical bypass distinguished its essential role in FeS cluster assembly from organelle maintenance, showing that unlike SufS, SufC loss does not destroy the apicoplast or its genome.\",\n      \"evidence\": \"Conditional gene deletion with IPP chemical bypass, apicoplast fluorescence microscopy, and organellar genome PCR in P. falciparum\",\n      \"pmids\": [\"37166116\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The essential FeS-dependent downstream client(s) causing lethality not identified\", \"Mechanistic reason for the divergent phenotype from SufS not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The essential downstream [Fe-S] cluster recipient proteins whose maturation depends on SufC, and the structural coupling between SufC ATP hydrolysis and cluster assembly/transfer, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No client apoprotein of the SufBC2D scaffold identified in the corpus\", \"No structure of the P. falciparum SufBC2D complex\", \"Mechanism linking ATPase cycle to cluster transfer unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0016226\", \"supporting_discovery_ids\": [3, 5]},\n      {\"term_id\": \"GO:0005524\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016226\", \"supporting_discovery_ids\": [2, 3, 5]}\n    ],\n    \"complexes\": [\n      \"SufB\\u2013SufC2\\u2013SufD [4Fe-4S] cluster assembly scaffold complex\",\n      \"SufBC complex\"\n    ],\n    \"partners\": [\n      \"SufB (apicoplast-genome-encoded)\",\n      \"SufD (apicoplast-targeted)\"\n    ],\n    \"other_free_text\": [\n      \"Nuclear-encoded, imported into the apicoplast\",\n      \"Essential for asexual blood-stage survival in both P. falciparum and P. berghei\",\n      \"SufD stimulates SufC ATPase activity\",\n      \"Essentiality attributable to FeS cluster assembly, not apicoplast organelle/genome maintenance (contrasts with SufS)\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1413500","name":null,"product":"iron-sulfur cluster assembly protein SufC","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1029200","name":null,"product":"iron-sulfur cluster assembly protein SufC","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1344800","name":null,"product":"iron-sulfur cluster assembly protein SufC, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SufC","evaluation":null}