{"gene":"PF3D7_1224200","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2021,"finding":"PF3D7_1224200 (BRO1/PfBro1) functions as part of an alternative ESCRT-III recruitment pathway in P. falciparum, working together with PfVps32 and PfVps60 to mediate extracellular vesicle production; purified recombinant PfBro1 protein reconstituted multivesicular body formation and membrane shedding in giant unilamellar vesicle membrane models, and PfBro1 was detected in EVs purified from parasitized red blood cell cultures by super-resolution microscopy and dot blot assays.","method":"Reconstitution with purified recombinant proteins in giant unilamellar vesicles (GUV membrane model); super-resolution microscopy; dot blot assays on purified EVs; genetic disruption (PfVps60 KO) revealing redistribution of ESCRT-III components including PfBro1","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro reconstitution with purified recombinant protein plus orthogonal localization methods (super-resolution microscopy, dot blot), single lab study","pmids":["33798247"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1224200 (BRO1/PfBro1) is a component of P. falciparum's functional ESCRT-III machinery, participating in an alternative ESCRT-III recruitment pathway alongside PfVps32 and PfVps60 to drive extracellular vesicle production and membrane remodeling during the asexual intraerythrocytic life cycle, as demonstrated by in vitro reconstitution and detection of PfBro1 within secreted EVs."},"narrative":{"mechanistic_narrative":"PF3D7_1224200 (BRO1/PfBro1) is a BRO1 domain-containing component of the Plasmodium falciparum ESCRT-III machinery that participates in an alternative ESCRT-III recruitment pathway driving extracellular vesicle production and membrane remodeling [PMID:33798247]. Working together with PfVps32 and PfVps60, purified recombinant PfBro1 reconstitutes multivesicular body formation and membrane shedding in giant unilamellar vesicle membrane models, and PfBro1 is detected within extracellular vesicles purified from parasitized red blood cell cultures [PMID:33798247]. Beyond this single reconstitution and localization study, no further mechanistic detail — including binding partners, recruitment mechanism, or in vivo genetic requirement of PfBro1 itself — has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"It was unknown whether P. falciparum possessed a functional BRO1-associated ESCRT-III pathway capable of remodeling membranes; reconstitution established that PfBro1 acts within an alternative ESCRT-III recruitment route to drive extracellular vesicle biogenesis.","evidence":"in vitro reconstitution with purified recombinant PfBro1 in giant unilamellar vesicles, plus super-resolution microscopy and dot blot detection of PfBro1 in purified EVs, with PfVps60 KO showing redistribution of ESCRT-III components","pmids":["33798247"],"confidence":"Medium","gaps":["no direct binding partner of PfBro1 identified or reciprocal interaction validated","no genetic disruption of PfBro1 itself to establish its requirement for EV production in vivo","mechanism by which PfBro1 is recruited to membranes not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PfBro1 is recruited to sites of membrane remodeling and whether it is essential for extracellular vesicle production during the intraerythrocytic cycle remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no loss-of-function study targeting PF3D7_1224200 directly","no structural model of PfBro1 or its membrane-binding interface","functional role of EVs produced via this pathway during infection not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["ESCRT-III machinery (alternative recruitment pathway, with PfVps32 and PfVps60)"],"partners":["PFVPS32","PFVPS60"],"other_free_text":["Reconstitutes multivesicular body formation and membrane shedding in giant unilamellar vesicle models [#0]","Detected within extracellular vesicles purified from parasitized red blood cell cultures [#0]","PfVps60 knockout leads to redistribution of ESCRT-III components including PfBro1 [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"33798247","id":"PMC_33798247","title":"The ESCRT-III machinery participates in the production of extracellular vesicles and protein export during Plasmodium falciparum infection.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/33798247","citation_count":43,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfBRO1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3439,"output_tokens":523,"usd":0.009081,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5034,"output_tokens":1296,"usd":0.028785,"stage2_stop_reason":"end_turn"},"total_usd":0.037866,"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\": 2021,\n      \"finding\": \"PF3D7_1224200 (BRO1/PfBro1) functions as part of an alternative ESCRT-III recruitment pathway in P. falciparum, working together with PfVps32 and PfVps60 to mediate extracellular vesicle production; purified recombinant PfBro1 protein reconstituted multivesicular body formation and membrane shedding in giant unilamellar vesicle membrane models, and PfBro1 was detected in EVs purified from parasitized red blood cell cultures by super-resolution microscopy and dot blot assays.\",\n      \"method\": \"Reconstitution with purified recombinant proteins in giant unilamellar vesicles (GUV membrane model); super-resolution microscopy; dot blot assays on purified EVs; genetic disruption (PfVps60 KO) revealing redistribution of ESCRT-III components including PfBro1\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro reconstitution with purified recombinant protein plus orthogonal localization methods (super-resolution microscopy, dot blot), single lab study\",\n      \"pmids\": [\"33798247\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1224200 (BRO1/PfBro1) is a component of P. falciparum's functional ESCRT-III machinery, participating in an alternative ESCRT-III recruitment pathway alongside PfVps32 and PfVps60 to drive extracellular vesicle production and membrane remodeling during the asexual intraerythrocytic life cycle, as demonstrated by in vitro reconstitution and detection of PfBro1 within secreted EVs.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1224200 (BRO1/PfBro1) is a BRO1 domain-containing component of the Plasmodium falciparum ESCRT-III machinery that participates in an alternative ESCRT-III recruitment pathway driving extracellular vesicle production and membrane remodeling [#0]. Working together with PfVps32 and PfVps60, purified recombinant PfBro1 reconstitutes multivesicular body formation and membrane shedding in giant unilamellar vesicle membrane models, and PfBro1 is detected within extracellular vesicles purified from parasitized red blood cell cultures [#0]. Beyond this single reconstitution and localization study, no further mechanistic detail — including binding partners, recruitment mechanism, or in vivo genetic requirement of PfBro1 itself — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"It was unknown whether P. falciparum possessed a functional BRO1-associated ESCRT-III pathway capable of remodeling membranes; reconstitution established that PfBro1 acts within an alternative ESCRT-III recruitment route to drive extracellular vesicle biogenesis.\",\n      \"evidence\": \"in vitro reconstitution with purified recombinant PfBro1 in giant unilamellar vesicles, plus super-resolution microscopy and dot blot detection of PfBro1 in purified EVs, with PfVps60 KO showing redistribution of ESCRT-III components\",\n      \"pmids\": [\"33798247\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no direct binding partner of PfBro1 identified or reciprocal interaction validated\",\n        \"no genetic disruption of PfBro1 itself to establish its requirement for EV production in vivo\",\n        \"mechanism by which PfBro1 is recruited to membranes not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PfBro1 is recruited to sites of membrane remodeling and whether it is essential for extracellular vesicle production during the intraerythrocytic cycle remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no loss-of-function study targeting PF3D7_1224200 directly\",\n        \"no structural model of PfBro1 or its membrane-binding interface\",\n        \"functional role of EVs produced via this pathway during infection not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0032266\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:1903561\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0032509\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"ESCRT-III machinery (alternative recruitment pathway, with PfVps32 and PfVps60)\"\n    ],\n    \"partners\": [\n      \"PfVps32\",\n      \"PfVps60\"\n    ],\n    \"other_free_text\": [\n      \"Reconstitutes multivesicular body formation and membrane shedding in giant unilamellar vesicle models [#0]\",\n      \"Detected within extracellular vesicles purified from parasitized red blood cell cultures [#0]\",\n      \"PfVps60 knockout leads to redistribution of ESCRT-III components including PfBro1 [#0]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1224200","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_1441800). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1224200","name":null,"product":"BRO1 domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1439100","name":null,"product":"BRO1 domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1443400","name":null,"product":"BRO1 domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}