{"gene":"PF3D7_1119600","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2026,"finding":"P. falciparum FtsH (PF3D7_1119600), a zinc-dependent metalloprotease, was identified as a likely interaction partner of stomatin-like protein (STOML) by pulldown experiments. The predicted AlphaFold2 structure of STOML resembles bacterial HflK/C, which forms a vault-like structure around bacterial FtsH hexamers, suggesting a similar STOML-FtsH complex in P. falciparum. This complex localizes to specific loci (branching points and endings) of the asexual blood-stage mitochondrial network.","method":"Pulldown (Co-IP/affinity purification of epitope-tagged STOML with mass spectrometry identification of FtsH); AlphaFold2 structural prediction; live imaging of epitope-tagged endogenous proteins","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single pulldown identifying FtsH as interaction partner, supported by structural prediction and localization imaging, but no reciprocal Co-IP or in vitro reconstitution of the complex; single lab","pmids":["41662436"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum FtsH (PF3D7_1119600) is a zinc-dependent ATP-dependent metalloprotease that localizes to specific loci on the mitochondrial network and likely forms a complex with the SPFH-family stomatin-like protein (STOML), analogous to the bacterial HflK/C–FtsH vault complex, potentially facilitating asexual blood-stage parasite development."},"narrative":{"mechanistic_narrative":"P. falciparum FtsH (PF3D7_1119600) is a zinc-dependent metalloprotease identified as a likely interaction partner of the stomatin-like protein (STOML) through affinity purification of epitope-tagged STOML, with the complex localizing to specific loci—branching points and endings—of the asexual blood-stage mitochondrial network [PMID:41662436]. AlphaFold2 prediction indicates STOML structurally resembles bacterial HflK/C, which forms a vault-like assembly around FtsH hexamers, raising the possibility of an analogous STOML–FtsH complex in the parasite [PMID:41662436]. Beyond this single association study, no further mechanistic detail—including protease substrates, ATPase activity, or the functional consequence of the interaction—has been characterized in the available corpus.","teleology":[{"year":2026,"claim":"To place a putative parasite FtsH metalloprotease into a functional context, this work asked what it interacts with and where it acts, establishing FtsH as a candidate partner of STOML at defined mitochondrial network loci.","evidence":"Pulldown/Co-IP of epitope-tagged STOML with mass spectrometry, AlphaFold2 structural prediction, and live imaging of epitope-tagged endogenous proteins in P. falciparum","pmids":["41662436"],"confidence":"Medium","gaps":["No reciprocal Co-IP or in vitro reconstitution confirming a direct STOML–FtsH complex","No demonstration of FtsH protease or ATPase activity, nor identification of substrates","Functional requirement of FtsH for blood-stage development not tested (e.g. by knockdown/knockout)"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether the STOML–FtsH association is direct and vault-forming as in bacteria, and what FtsH proteolyzes to influence mitochondrial function, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Direct binding and stoichiometry of the proposed complex unproven","No substrate or enzymatic characterization of PF3D7_1119600","Physiological role in parasite mitochondrial biology undetermined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Putative STOML–FtsH complex (analogous to bacterial HflK/C–FtsH vault) [#0]"],"partners":["STOMATIN-LIKE PROTEIN (STOML) [#0]"],"other_free_text":["Identified as a likely STOML interaction partner by pulldown/mass spectrometry [#0]","Localizes to branching points and endings of the asexual blood-stage mitochondrial network [#0]","STOML predicted (AlphaFold2) to resemble bacterial HflK/C, suggesting a vault-like assembly around FtsH hexamers [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"33497624","id":"PMC_33497624","title":"Structure, function, and substrates of Clp AAA+ protease systems in cyanobacteria, plastids, and apicoplasts: A comparative analysis.","date":"2021","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/33497624","citation_count":58,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP","FTSH"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41662436","id":"PMC_41662436","title":"Plasmodium falciparum stomatin-like protein forms a putative complex with a metalloprotease in distinct mitochondrial loci.","date":"2026","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/41662436","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["FTSH"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3916,"output_tokens":475,"usd":0.009437,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4968,"output_tokens":1265,"usd":0.028233,"stage2_stop_reason":"end_turn"},"total_usd":0.03767,"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\": 2026,\n      \"finding\": \"P. falciparum FtsH (PF3D7_1119600), a zinc-dependent metalloprotease, was identified as a likely interaction partner of stomatin-like protein (STOML) by pulldown experiments. The predicted AlphaFold2 structure of STOML resembles bacterial HflK/C, which forms a vault-like structure around bacterial FtsH hexamers, suggesting a similar STOML-FtsH complex in P. falciparum. This complex localizes to specific loci (branching points and endings) of the asexual blood-stage mitochondrial network.\",\n      \"method\": \"Pulldown (Co-IP/affinity purification of epitope-tagged STOML with mass spectrometry identification of FtsH); AlphaFold2 structural prediction; live imaging of epitope-tagged endogenous proteins\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single pulldown identifying FtsH as interaction partner, supported by structural prediction and localization imaging, but no reciprocal Co-IP or in vitro reconstitution of the complex; single lab\",\n      \"pmids\": [\"41662436\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"P. falciparum FtsH (PF3D7_1119600) is a zinc-dependent ATP-dependent metalloprotease that localizes to specific loci on the mitochondrial network and likely forms a complex with the SPFH-family stomatin-like protein (STOML), analogous to the bacterial HflK/C–FtsH vault complex, potentially facilitating asexual blood-stage parasite development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"P. falciparum FtsH (PF3D7_1119600) is a zinc-dependent metalloprotease identified as a likely interaction partner of the stomatin-like protein (STOML) through affinity purification of epitope-tagged STOML, with the complex localizing to specific loci—branching points and endings—of the asexual blood-stage mitochondrial network [#0]. AlphaFold2 prediction indicates STOML structurally resembles bacterial HflK/C, which forms a vault-like assembly around FtsH hexamers, raising the possibility of an analogous STOML–FtsH complex in the parasite [#0]. Beyond this single association study, no further mechanistic detail—including protease substrates, ATPase activity, or the functional consequence of the interaction—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2026,\n      \"claim\": \"To place a putative parasite FtsH metalloprotease into a functional context, this work asked what it interacts with and where it acts, establishing FtsH as a candidate partner of STOML at defined mitochondrial network loci.\",\n      \"evidence\": \"Pulldown/Co-IP of epitope-tagged STOML with mass spectrometry, AlphaFold2 structural prediction, and live imaging of epitope-tagged endogenous proteins in P. falciparum\",\n      \"pmids\": [\"41662436\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reciprocal Co-IP or in vitro reconstitution confirming a direct STOML–FtsH complex\",\n        \"No demonstration of FtsH protease or ATPase activity, nor identification of substrates\",\n        \"Functional requirement of FtsH for blood-stage development not tested (e.g. by knockdown/knockout)\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the STOML–FtsH association is direct and vault-forming as in bacteria, and what FtsH proteolyzes to influence mitochondrial function, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct binding and stoichiometry of the proposed complex unproven\",\n        \"No substrate or enzymatic characterization of PF3D7_1119600\",\n        \"Physiological role in parasite mitochondrial biology undetermined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004222\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008270\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"Putative STOML–FtsH complex (analogous to bacterial HflK/C–FtsH vault) [#0]\"],\n    \"partners\": [\"Stomatin-like protein (STOML) [#0]\"],\n    \"other_free_text\": [\n      \"Identified as a likely STOML interaction partner by pulldown/mass spectrometry [#0]\",\n      \"Localizes to branching points and endings of the asexual blood-stage mitochondrial network [#0]\",\n      \"STOML predicted (AlphaFold2) to resemble bacterial HflK/C, suggesting a vault-like assembly around FtsH hexamers [#0]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1119600","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_0318100, PF3D7_0416600). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1119600","name":null,"product":"ATP-dependent zinc metalloprotease FTSH, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0928500","name":null,"product":"ATP-dependent zinc metalloprotease FTSH, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0917300","name":null,"product":"ATP-dependent zinc metalloprotease FTSH, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}