{"gene":"PF3D7_API04700","run_date":"2026-09-08T15:24:04","timeline":{"discoveries":[{"year":2003,"finding":"PF3D7_API04700 (SufB), encoded by the apicoplast genome of P. falciparum, physically interacts with its partner SufC (ycf16), a nuclear-encoded ATPase imported into the plastid, as demonstrated by experimental evidence of a physical interaction between the two proteins.","method":"Physical interaction assay (experimental evidence of SufB–SufC interaction reported)","journal":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct interaction demonstrated experimentally, but method details are limited in the abstract; replicated later by independent study (PMID:21722645)","pmids":["12594924"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"PF3D7_API04700 (apicoplast-encoded PfSufB) interacts with nuclear-encoded PfSufC, as shown by in vitro interaction using an internal region of PfSufB and co-elution of endogenous PfSufB from parasite lysate with recombinant PfSufC on an affinity column. Unlike bacterial SufB but similar to plant plastid SufB, recombinant apicoplast PfSufB exhibited ATPase activity, indicating evolution of specialized function in the plastid counterpart.","method":"In vitro interaction assay (pulldown with internal SufB fragment), affinity co-elution from parasite lysate, ATPase activity assay with recombinant protein","journal":"International journal for parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (in vitro binding, co-elution from native lysate, enzymatic assay) in a single focused study; findings replicated the interaction seen in PMID:12594924","pmids":["21722645"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PF3D7_API04700 (apicoplast-encoded PfSufB) forms a complex with apicoplast-targeted PfSufC and PfSufD, as shown by in vitro interaction experiments and in vivo cross-linking. The PfSufB–PfSufC2–PfSufD complex functions as a scaffold capable of assembling [4Fe-4S] clusters in vitro.","method":"In vitro interaction assays, in vivo cross-linking, in vitro [4Fe-4S] cluster assembly assay","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro scaffold activity (cluster assembly) combined with in vivo cross-linking and in vitro interaction, multiple orthogonal methods in a single focused study","pmids":["28695709"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_API04700 (SufB) is an apicoplast genome-encoded component of the SUF iron-sulfur cluster assembly pathway in P. falciparum: it physically interacts with the nuclear-encoded ATPases PfSufC and PfSufD to form a PfSufB–PfSufC2–PfSufD scaffold complex that assembles [4Fe-4S] clusters in vitro, and unlike its bacterial homolog, PfSufB itself displays ATPase activity consistent with a specialized function evolved in the plastid."},"narrative":{"mechanistic_narrative":"PF3D7_API04700 (SufB) is an apicoplast genome-encoded scaffold component of the SUF iron-sulfur cluster assembly pathway in Plasmodium falciparum [PMID:12594924, PMID:28695709]. It physically interacts with the nuclear-encoded, plastid-imported ATPase PfSufC, an association demonstrated both by in vitro binding of an internal PfSufB region and by co-elution of endogenous PfSufB from parasite lysate with recombinant PfSufC [PMID:12594924, PMID:21722645]. Together with PfSufD, PfSufB and PfSufC form a PfSufB–PfSufC2–PfSufD complex that functions as a scaffold capable of assembling [4Fe-4S] clusters in vitro, as shown by in vitro interaction assays, in vivo cross-linking, and reconstituted cluster assembly [PMID:28695709]. Distinct from its bacterial homolog but resembling plant plastid SufB, recombinant apicoplast PfSufB itself exhibits ATPase activity, indicating a specialized function evolved in the plastid counterpart [PMID:21722645]. Beyond its role as the scaffold subunit of this complex and its intrinsic ATPase activity, no further mechanistic detail for PF3D7_API04700 has been characterized in the available corpus.","teleology":[{"year":2003,"claim":"Establishing that the apicoplast genome-encoded SufB physically engages a nuclear-encoded partner was the first evidence that the apicoplast SUF machinery is assembled from proteins of two genomes.","evidence":"Physical interaction assay showing PfSufB (apicoplast-encoded) binds the imported ATPase PfSufC in P. falciparum","pmids":["12594924"],"confidence":"Medium","gaps":["Method details limited; binding interface and stoichiometry not defined","No functional consequence of the interaction demonstrated","Involvement of additional subunits not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Confirming the PfSufB–PfSufC interaction with orthogonal methods and demonstrating intrinsic ATPase activity in PfSufB established that the apicoplast scaffold subunit has a specialized enzymatic property absent in bacterial SufB.","evidence":"In vitro pulldown with an internal PfSufB fragment, affinity co-elution of endogenous PfSufB from parasite lysate, and ATPase assay with recombinant protein in P. falciparum","pmids":["21722645"],"confidence":"High","gaps":["Structural basis and residues of PfSufB ATPase activity not defined","Functional role of PfSufB ATPase within the assembly cycle unresolved","Whether SufD is part of the interaction not tested here"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Reconstituting a PfSufB–PfSufC2–PfSufD complex that assembles [4Fe-4S] clusters in vitro established PfSufB as the scaffold subunit on which apicoplast iron-sulfur clusters are built.","evidence":"In vitro interaction assays, in vivo cross-linking, and in vitro [4Fe-4S] cluster assembly assay in P. falciparum","pmids":["28695709"],"confidence":"High","gaps":["Mechanism of cluster transfer from the scaffold to downstream acceptors not defined","Role of PfSufB ATPase activity in the assembly reaction not established","In vivo essentiality and phenotype of PfSufB not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PfSufB's ATPase activity is coupled to cluster assembly and how the assembled [4Fe-4S] clusters are delivered to downstream apicoplast targets remain unknown.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of the PfSufB–PfSufC2–PfSufD complex","No downstream cluster acceptor identified","Genetic requirement of PfSufB in parasite viability not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfSufB–PfSufC2–PfSufD scaffold complex"],"partners":["PFSUFC (YCF16, NUCLEAR-ENCODED ATPASE)","PFSUFD (APICOPLAST-TARGETED)"],"other_free_text":["PF3D7_API04700 (SufB) is encoded by the apicoplast genome, whereas its partners PfSufC and PfSufD are nuclear-encoded and imported into the plastid [#0, #2]","Unlike bacterial SufB, apicoplast PfSufB exhibits intrinsic ATPase activity resembling plant plastid SufB [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"11555280","id":"PMC_11555280","title":"Nifs and Sufs in malaria.","date":"2001","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/11555280","citation_count":80,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUFB"],"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":["SUFB"],"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":["curated_ref"],"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":["SUFB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27033210","id":"PMC_27033210","title":"Structural and functional characterization of an iron-sulfur cluster assembly scaffold protein-SufA from Plasmodium vivax.","date":"2016","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/27033210","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUFB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22266119","id":"PMC_22266119","title":"Plasmodium vivax apicoplast genome: a comparative analysis of major genes from Indian field isolates.","date":"2012","source":"Acta tropica","url":"https://pubmed.ncbi.nlm.nih.gov/22266119","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUFB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5503,"output_tokens":1012,"usd":0.015845,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5793,"output_tokens":2180,"usd":0.041732,"stage2_stop_reason":"end_turn"},"total_usd":0.057577,"stage1_batch_id":"msgbatch_01S4WrhSkksYHeZXxqf3za3o","stage2_batch_id":"msgbatch_019VBBeuW6G52X8gZfsFDfb5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"PF3D7_API04700 (SufB), encoded by the apicoplast genome of P. falciparum, physically interacts with its partner SufC (ycf16), a nuclear-encoded ATPase imported into the plastid, as demonstrated by experimental evidence of a physical interaction between the two proteins.\",\n      \"method\": \"Physical interaction assay (experimental evidence of SufB–SufC interaction reported)\",\n      \"journal\": \"Philosophical transactions of the Royal Society of London. Series B, Biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct interaction demonstrated experimentally, but method details are limited in the abstract; replicated later by independent study (PMID:21722645)\",\n      \"pmids\": [\"12594924\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PF3D7_API04700 (apicoplast-encoded PfSufB) interacts with nuclear-encoded PfSufC, as shown by in vitro interaction using an internal region of PfSufB and co-elution of endogenous PfSufB from parasite lysate with recombinant PfSufC on an affinity column. Unlike bacterial SufB but similar to plant plastid SufB, recombinant apicoplast PfSufB exhibited ATPase activity, indicating evolution of specialized function in the plastid counterpart.\",\n      \"method\": \"In vitro interaction assay (pulldown with internal SufB fragment), affinity co-elution from parasite lysate, ATPase activity assay with recombinant protein\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (in vitro binding, co-elution from native lysate, enzymatic assay) in a single focused study; findings replicated the interaction seen in PMID:12594924\",\n      \"pmids\": [\"21722645\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PF3D7_API04700 (apicoplast-encoded PfSufB) forms a complex with apicoplast-targeted PfSufC and PfSufD, as shown by in vitro interaction experiments and in vivo cross-linking. The PfSufB–PfSufC2–PfSufD complex functions as a scaffold capable of assembling [4Fe-4S] clusters in vitro.\",\n      \"method\": \"In vitro interaction assays, in vivo cross-linking, in vitro [4Fe-4S] cluster assembly assay\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro scaffold activity (cluster assembly) combined with in vivo cross-linking and in vitro interaction, multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"28695709\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_API04700 (SufB) is an apicoplast genome-encoded component of the SUF iron-sulfur cluster assembly pathway in P. falciparum: it physically interacts with the nuclear-encoded ATPases PfSufC and PfSufD to form a PfSufB–PfSufC2–PfSufD scaffold complex that assembles [4Fe-4S] clusters in vitro, and unlike its bacterial homolog, PfSufB itself displays ATPase activity consistent with a specialized function evolved in the plastid.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_API04700 (SufB) is an apicoplast genome-encoded scaffold component of the SUF iron-sulfur cluster assembly pathway in Plasmodium falciparum [#0, #2]. It physically interacts with the nuclear-encoded, plastid-imported ATPase PfSufC, an association demonstrated both by in vitro binding of an internal PfSufB region and by co-elution of endogenous PfSufB from parasite lysate with recombinant PfSufC [#0, #1]. Together with PfSufD, PfSufB and PfSufC form a PfSufB\\u2013PfSufC2\\u2013PfSufD complex that functions as a scaffold capable of assembling [4Fe-4S] clusters in vitro, as shown by in vitro interaction assays, in vivo cross-linking, and reconstituted cluster assembly [#2]. Distinct from its bacterial homolog but resembling plant plastid SufB, recombinant apicoplast PfSufB itself exhibits ATPase activity, indicating a specialized function evolved in the plastid counterpart [#1]. Beyond its role as the scaffold subunit of this complex and its intrinsic ATPase activity, no further mechanistic detail for PF3D7_API04700 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing that the apicoplast genome-encoded SufB physically engages a nuclear-encoded partner was the first evidence that the apicoplast SUF machinery is assembled from proteins of two genomes.\",\n      \"evidence\": \"Physical interaction assay showing PfSufB (apicoplast-encoded) binds the imported ATPase PfSufC in P. falciparum\",\n      \"pmids\": [\"12594924\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Method details limited; binding interface and stoichiometry not defined\",\n        \"No functional consequence of the interaction demonstrated\",\n        \"Involvement of additional subunits not addressed\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Confirming the PfSufB\\u2013PfSufC interaction with orthogonal methods and demonstrating intrinsic ATPase activity in PfSufB established that the apicoplast scaffold subunit has a specialized enzymatic property absent in bacterial SufB.\",\n      \"evidence\": \"In vitro pulldown with an internal PfSufB fragment, affinity co-elution of endogenous PfSufB from parasite lysate, and ATPase assay with recombinant protein in P. falciparum\",\n      \"pmids\": [\"21722645\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Structural basis and residues of PfSufB ATPase activity not defined\",\n        \"Functional role of PfSufB ATPase within the assembly cycle unresolved\",\n        \"Whether SufD is part of the interaction not tested here\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Reconstituting a PfSufB\\u2013PfSufC2\\u2013PfSufD complex that assembles [4Fe-4S] clusters in vitro established PfSufB as the scaffold subunit on which apicoplast iron-sulfur clusters are built.\",\n      \"evidence\": \"In vitro interaction assays, in vivo cross-linking, and in vitro [4Fe-4S] cluster assembly assay in P. falciparum\",\n      \"pmids\": [\"28695709\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Mechanism of cluster transfer from the scaffold to downstream acceptors not defined\",\n        \"Role of PfSufB ATPase activity in the assembly reaction not established\",\n        \"In vivo essentiality and phenotype of PfSufB not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PfSufB's ATPase activity is coupled to cluster assembly and how the assembled [4Fe-4S] clusters are delivered to downstream apicoplast targets remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No structural model of the PfSufB\\u2013PfSufC2\\u2013PfSufD complex\",\n        \"No downstream cluster acceptor identified\",\n        \"Genetic requirement of PfSufB in parasite viability not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0016226\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0051536\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009507\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016226\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"PfSufB\\u2013PfSufC2\\u2013PfSufD scaffold complex\"\n    ],\n    \"partners\": [\n      \"PfSufC (ycf16, nuclear-encoded ATPase)\",\n      \"PfSufD (apicoplast-targeted)\"\n    ],\n    \"other_free_text\": [\n      \"PF3D7_API04700 (SufB) is encoded by the apicoplast genome, whereas its partners PfSufC and PfSufD are nuclear-encoded and imported into the plastid [#0, #2]\",\n      \"Unlike bacterial SufB, apicoplast PfSufB exhibits intrinsic ATPase activity resembling plant plastid SufB [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_API04700","name":null,"product":"iron-sulfur cluster assembly protein SufB","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SUFB","evaluation":null}