{"gene":"TG_231410","gene_symbol":"ICAP2","run_date":"2026-09-08T11:06:51","timeline":{"discoveries":[{"year":2018,"finding":"ICAP2 is a previously unknown subunit of the Toxoplasma gondii mitochondrial ATP synthase complex. Modeling suggests ICAP2 is distantly related to mammalian stator subunits. Co-immunoprecipitation and complex analysis confirmed ICAP2 forms part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the ATP synthase complex, establishing ICAP2 as an essential structural component of the Toxoplasma ATP synthase.","method":"Protein complex identification, structural modeling, co-immunoprecipitation, conditional depletion (knockdown) with phenotypic readouts (mitochondrial morphology, oxygen consumption, complex assembly)","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal complex confirmation, conditional depletion with multiple orthogonal phenotypic readouts (morphology, respiration, complex disassembly) in a single rigorous study","pmids":["30204085"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"ICAP2 is a Toxoplasma gondii-specific subunit of the mitochondrial ATP synthase that functions as a stator-like component, where its depletion causes ATP synthase complex disassembly, decreased oxygen consumption, and aberrant mitochondrial morphology, indicating it is essential for maintaining ATP synthase structural integrity and mitochondrial function."},"narrative":{"mechanistic_narrative":"ICAP2 is a Toxoplasma gondii-specific subunit of the mitochondrial ATP synthase complex, where it acts as a structural component required for complex integrity and mitochondrial function [PMID:30204085]. Structural modeling places it as distantly related to mammalian stator subunits, and co-immunoprecipitation confirms its physical incorporation into the ATP synthase complex [PMID:30204085]. Conditional depletion of ICAP2 disassembles the ATP synthase complex and produces aberrant mitochondrial morphology and decreased oxygen consumption, establishing that it is essential for maintaining ATP synthase assembly and oxidative respiration [PMID:30204085]. Beyond this single characterization [PMID:30204085], no further mechanistic detail has been established in the available corpus.","teleology":[{"year":2018,"claim":"It was unknown which subunits maintain the structural integrity of the divergent Toxoplasma ATP synthase; identifying ICAP2 as a stator-like subunit established a specific structural determinant of complex assembly and mitochondrial respiration.","evidence":"Protein complex identification, structural modeling, co-immunoprecipitation, and conditional depletion with mitochondrial morphology, oxygen consumption, and complex-assembly readouts in Toxoplasma gondii","pmids":["30204085"],"confidence":"High","gaps":["The precise molecular interactions ICAP2 makes within the ATP synthase (which subunits it contacts) are not resolved","No structural model beyond distant homology to mammalian stator subunits","Whether ICAP2 has roles outside ATP synthase assembly is not addressed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The atomic-level architecture of ICAP2 within the ATP synthase and its direct binding partners remain undefined.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of the ICAP2-containing ATP synthase","Direct binding partners within the complex not mapped","Functional conservation across apicomplexan species not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial ATP synthase complex"],"partners":[],"other_free_text":["Toxoplasma-specific subunit distantly related to mammalian stator subunits [#0]","Depletion causes ATP synthase disassembly, aberrant mitochondrial morphology, and decreased oxygen consumption [#0]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"8579614","id":"PMC_8579614","title":"Purification and cloning of a soluble ATP-diphosphohydrolase (apyrase) from potato tubers (Solanum tuberosum).","date":"1996","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8579614","citation_count":263,"is_preprint":false},{"pmid":"25879281","id":"PMC_25879281","title":"The NLRP1 inflammasomes.","date":"2015","source":"Immunological reviews","url":"https://pubmed.ncbi.nlm.nih.gov/25879281","citation_count":200,"is_preprint":false},{"pmid":"30204085","id":"PMC_30204085","title":"Identification of cryptic subunits from an apicomplexan ATP synthase.","date":"2018","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/30204085","citation_count":53,"is_preprint":false},{"pmid":"30685461","id":"PMC_30685461","title":"Drug Resistance in Protozoan Parasites: An Incessant Wrestle for Survival.","date":"2019","source":"Journal of global antimicrobial resistance","url":"https://pubmed.ncbi.nlm.nih.gov/30685461","citation_count":37,"is_preprint":false},{"pmid":"41789725","id":"PMC_41789725","title":"Unconventional model organisms bend our view on mitochondrial cristae.","date":"2026","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/41789725","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4277,"output_tokens":436,"usd":0.009685,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5095,"output_tokens":1231,"usd":0.028125,"stage2_stop_reason":"end_turn"},"total_usd":0.03781,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"ICAP2 is a previously unknown subunit of the Toxoplasma gondii mitochondrial ATP synthase complex. Modeling suggests ICAP2 is distantly related to mammalian stator subunits. Co-immunoprecipitation and complex analysis confirmed ICAP2 forms part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the ATP synthase complex, establishing ICAP2 as an essential structural component of the Toxoplasma ATP synthase.\",\n      \"method\": \"Protein complex identification, structural modeling, co-immunoprecipitation, conditional depletion (knockdown) with phenotypic readouts (mitochondrial morphology, oxygen consumption, complex assembly)\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal complex confirmation, conditional depletion with multiple orthogonal phenotypic readouts (morphology, respiration, complex disassembly) in a single rigorous study\",\n      \"pmids\": [\"30204085\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ICAP2 is a Toxoplasma gondii-specific subunit of the mitochondrial ATP synthase that functions as a stator-like component, where its depletion causes ATP synthase complex disassembly, decreased oxygen consumption, and aberrant mitochondrial morphology, indicating it is essential for maintaining ATP synthase structural integrity and mitochondrial function.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ICAP2 is a Toxoplasma gondii-specific subunit of the mitochondrial ATP synthase complex, where it acts as a structural component required for complex integrity and mitochondrial function [#0]. Structural modeling places it as distantly related to mammalian stator subunits, and co-immunoprecipitation confirms its physical incorporation into the ATP synthase complex [#0]. Conditional depletion of ICAP2 disassembles the ATP synthase complex and produces aberrant mitochondrial morphology and decreased oxygen consumption, establishing that it is essential for maintaining ATP synthase assembly and oxidative respiration [#0]. Beyond this single characterization [#0], no further mechanistic detail has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"It was unknown which subunits maintain the structural integrity of the divergent Toxoplasma ATP synthase; identifying ICAP2 as a stator-like subunit established a specific structural determinant of complex assembly and mitochondrial respiration.\",\n      \"evidence\": \"Protein complex identification, structural modeling, co-immunoprecipitation, and conditional depletion with mitochondrial morphology, oxygen consumption, and complex-assembly readouts in Toxoplasma gondii\",\n      \"pmids\": [\"30204085\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The precise molecular interactions ICAP2 makes within the ATP synthase (which subunits it contacts) are not resolved\",\n        \"No structural model beyond distant homology to mammalian stator subunits\",\n        \"Whether ICAP2 has roles outside ATP synthase assembly is not addressed\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The atomic-level architecture of ICAP2 within the ATP synthase and its direct binding partners remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of the ICAP2-containing ATP synthase\",\n        \"Direct binding partners within the complex not mapped\",\n        \"Functional conservation across apicomplexan species not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0045259\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0042776\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Mitochondrial ATP synthase complex\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Toxoplasma-specific subunit distantly related to mammalian stator subunits [#0]\",\n      \"Depletion causes ATP synthase disassembly, aberrant mitochondrial morphology, and decreased oxygen consumption [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_231410","name":"ICAP2","product":"ATP synthase F0 subunit b-like protein","uniprot_acc":"A0A125YYF7","chromosome":"TGME49_chrVIII","start_pos":1406258},{"strain":"GT1","gene_id":"TGGT1_231410","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":1401693},{"strain":"RH88","gene_id":"TGRH88_075660","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023089","start_pos":6512466},{"strain":"VEG","gene_id":"TGVEG_231410","name":null,"product":"hypothetical protein","uniprot_acc":"B6KJK9","chromosome":"TGVEG_chrVIII","start_pos":1412455}]}