{"gene":"TG_240380","gene_symbol":"CGP","run_date":"2026-09-08T12:58:24","timeline":{"discoveries":[{"year":2022,"finding":"CGP (conoid gliding protein) is a novel conoid protein that functions late during egress and is required for the activation of gliding motility, as demonstrated by conditional knockout using the DiCre-system with an F-actin dynamics indicator strain.","method":"Conditional knockout (DiCre-system), splitCas9 phenotypic screen, F-actin dynamics indicator strain","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined cellular phenotype (gliding motility defect during egress), single lab, two complementary methods (screen + DiCre KO)","pmids":["35538310"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"finding":"CGP is essential for anchoring FRM1 and other preconoidal ring (PCR) components to mature PCRs; cryo-electron tomography of CGP-depleted parasites shows absence of PCRs in mature parasites, demonstrating CGP stabilises PCRs after replication but is not required for initial PCR assembly in daughter cells.","method":"Conditional depletion, cryo-electron tomography, co-immunoprecipitation/proximity labelling (CGP used as bait), fluorescence microscopy","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — cryo-ET structural validation combined with conditional depletion and interactome (bait) experiments, multiple orthogonal methods in one study","pmids":["41315181"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"finding":"Using CGP as bait, ASAF1 (APR scaffold assembly factor 1) was identified as a binding partner/interactor that defines the position of the conoid complex before tubulin polymerisation; depletion of ASAF1 results in failure of conoid complex assembly, disorganised microtubules, and lack of daughter cell formation.","method":"Affinity purification/co-immunoprecipitation using CGP as bait, conditional depletion of ASAF1, cryo-electron tomography","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal bait experiment identifying interaction, with functional validation by conditional KO, single lab","pmids":["41315181"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"CGP is an essential conoid protein in Toxoplasma gondii that localises to the preconoidal rings (PCRs), where it stabilises PCR integrity after replication by anchoring FRM1 and other PCR components to mature PCRs, and is required for the activation of gliding motility during late egress; CGP interacts with ASAF1, a scaffold factor that positions the conoid complex prior to tubulin polymerisation during daughter cell formation."},"narrative":{"mechanistic_narrative":"CGP (conoid gliding protein) is an essential conoid protein of Toxoplasma gondii that maintains the structural integrity of the preconoidal rings (PCRs) and is required for the activation of gliding motility during egress [PMID:35538310, PMID:41315181]. CGP acts late during egress, and its conditional knockout produces a gliding motility defect [PMID:35538310]. CGP stabilises PCRs after replication rather than driving their initial assembly: cryo-electron tomography of CGP-depleted parasites shows loss of PCRs in mature parasites while daughter-cell PCR assembly still occurs, and CGP is required to anchor FRM1 and other PCR components to mature PCRs [PMID:41315181]. Using CGP as bait, ASAF1 was identified as an interacting scaffold factor that defines the position of the conoid complex prior to tubulin polymerisation, and whose depletion abolishes conoid complex assembly, disorganises microtubules, and blocks daughter cell formation [PMID:41315181].","teleology":[{"year":2022,"claim":"Establishing that a previously uncharacterised conoid protein controls when parasites become motile, CGP was shown to act late in egress and to be required for activation of gliding motility.","evidence":"Conditional knockout (DiCre) plus splitCas9 phenotypic screen in an F-actin dynamics indicator strain of T. gondii","pmids":["35538310"],"confidence":"Medium","gaps":["The structural role of CGP at the conoid was not defined","Molecular partners of CGP were not identified","How the motility defect connects to conoid architecture was unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"claim":"Resolving where CGP acts structurally, cryo-ET and interactome analysis showed CGP stabilises preconoidal rings after replication and anchors FRM1 and other PCR components to mature PCRs without being needed for initial PCR assembly.","evidence":"Conditional depletion, cryo-electron tomography, and co-immunoprecipitation/proximity labelling with CGP as bait in T. gondii","pmids":["41315181"],"confidence":"High","gaps":["The mechanism by which CGP physically anchors FRM1 to PCRs is not defined","How loss of PCR integrity mechanistically causes the gliding defect is not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"claim":"Extending the CGP interactome, ASAF1 was identified as a CGP-associated scaffold factor that positions the conoid complex before tubulin polymerisation, linking CGP to early conoid/microtubule organisation during daughter cell formation.","evidence":"Affinity purification/co-IP with CGP as bait, conditional depletion of ASAF1, and cryo-electron tomography in T. gondii","pmids":["41315181"],"confidence":"Medium","gaps":["Direct versus indirect nature of the CGP–ASAF1 interaction is not resolved","Whether CGP itself contributes to conoid positioning through ASAF1 is not established","The molecular basis of ASAF1 scaffolding activity is uncharacterised"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical mechanism linking CGP-dependent PCR stabilisation to activation of gliding motility, and the structural basis of its interactions with FRM1 and ASAF1, remain open.","evidence":"No further mechanistic evidence in the available corpus","pmids":[],"confidence":"Medium","gaps":["No structural model of CGP within the PCR","No mapping of CGP binding interfaces to FRM1 or ASAF1","Mechanistic coupling of PCR integrity to motility activation not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Preconoidal ring (PCR) / conoid complex"],"partners":["FRM1","ASAF1"],"other_free_text":["CGP stabilises preconoidal rings after replication but is dispensable for initial PCR assembly in daughter cells [#1]","CGP is required for activation of gliding motility during late egress [#0]","ASAF1 depletion abolishes conoid complex assembly, disorganises microtubules, and blocks daughter cell formation [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"35538310","id":"PMC_35538310","title":"A splitCas9 phenotypic screen in Toxoplasma gondii identifies proteins involved in host cell egress and invasion.","date":"2022","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35538310","citation_count":35,"is_preprint":false},{"pmid":"41315181","id":"PMC_41315181","title":"An apical ring protein essential for conoid complex assembly and daughter cell formation in Toxoplasma gondii.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41315181","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3301,"output_tokens":861,"usd":0.011409,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5694,"output_tokens":2085,"usd":0.040297,"stage2_stop_reason":"end_turn"},"total_usd":0.051706,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"CGP (conoid gliding protein) is a novel conoid protein that functions late during egress and is required for the activation of gliding motility, as demonstrated by conditional knockout using the DiCre-system with an F-actin dynamics indicator strain.\",\n      \"method\": \"Conditional knockout (DiCre-system), splitCas9 phenotypic screen, F-actin dynamics indicator strain\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined cellular phenotype (gliding motility defect during egress), single lab, two complementary methods (screen + DiCre KO)\",\n      \"pmids\": [\"35538310\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CGP is essential for anchoring FRM1 and other preconoidal ring (PCR) components to mature PCRs; cryo-electron tomography of CGP-depleted parasites shows absence of PCRs in mature parasites, demonstrating CGP stabilises PCRs after replication but is not required for initial PCR assembly in daughter cells.\",\n      \"method\": \"Conditional depletion, cryo-electron tomography, co-immunoprecipitation/proximity labelling (CGP used as bait), fluorescence microscopy\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — cryo-ET structural validation combined with conditional depletion and interactome (bait) experiments, multiple orthogonal methods in one study\",\n      \"pmids\": [\"41315181\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Using CGP as bait, ASAF1 (APR scaffold assembly factor 1) was identified as a binding partner/interactor that defines the position of the conoid complex before tubulin polymerisation; depletion of ASAF1 results in failure of conoid complex assembly, disorganised microtubules, and lack of daughter cell formation.\",\n      \"method\": \"Affinity purification/co-immunoprecipitation using CGP as bait, conditional depletion of ASAF1, cryo-electron tomography\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal bait experiment identifying interaction, with functional validation by conditional KO, single lab\",\n      \"pmids\": [\"41315181\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CGP is an essential conoid protein in Toxoplasma gondii that localises to the preconoidal rings (PCRs), where it stabilises PCR integrity after replication by anchoring FRM1 and other PCR components to mature PCRs, and is required for the activation of gliding motility during late egress; CGP interacts with ASAF1, a scaffold factor that positions the conoid complex prior to tubulin polymerisation during daughter cell formation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CGP (conoid gliding protein) is an essential conoid protein of Toxoplasma gondii that maintains the structural integrity of the preconoidal rings (PCRs) and is required for the activation of gliding motility during egress [#0, #1]. CGP acts late during egress, and its conditional knockout produces a gliding motility defect [#0]. CGP stabilises PCRs after replication rather than driving their initial assembly: cryo-electron tomography of CGP-depleted parasites shows loss of PCRs in mature parasites while daughter-cell PCR assembly still occurs, and CGP is required to anchor FRM1 and other PCR components to mature PCRs [#1]. Using CGP as bait, ASAF1 was identified as an interacting scaffold factor that defines the position of the conoid complex prior to tubulin polymerisation, and whose depletion abolishes conoid complex assembly, disorganises microtubules, and blocks daughter cell formation [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Establishing that a previously uncharacterised conoid protein controls when parasites become motile, CGP was shown to act late in egress and to be required for activation of gliding motility.\",\n      \"evidence\": \"Conditional knockout (DiCre) plus splitCas9 phenotypic screen in an F-actin dynamics indicator strain of T. gondii\",\n      \"pmids\": [\n        \"35538310\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The structural role of CGP at the conoid was not defined\",\n        \"Molecular partners of CGP were not identified\",\n        \"How the motility defect connects to conoid architecture was unresolved\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Resolving where CGP acts structurally, cryo-ET and interactome analysis showed CGP stabilises preconoidal rings after replication and anchors FRM1 and other PCR components to mature PCRs without being needed for initial PCR assembly.\",\n      \"evidence\": \"Conditional depletion, cryo-electron tomography, and co-immunoprecipitation/proximity labelling with CGP as bait in T. gondii\",\n      \"pmids\": [\n        \"41315181\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The mechanism by which CGP physically anchors FRM1 to PCRs is not defined\",\n        \"How loss of PCR integrity mechanistically causes the gliding defect is not established\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extending the CGP interactome, ASAF1 was identified as a CGP-associated scaffold factor that positions the conoid complex before tubulin polymerisation, linking CGP to early conoid/microtubule organisation during daughter cell formation.\",\n      \"evidence\": \"Affinity purification/co-IP with CGP as bait, conditional depletion of ASAF1, and cryo-electron tomography in T. gondii\",\n      \"pmids\": [\n        \"41315181\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct versus indirect nature of the CGP\\u2013ASAF1 interaction is not resolved\",\n        \"Whether CGP itself contributes to conoid positioning through ASAF1 is not established\",\n        \"The molecular basis of ASAF1 scaffolding activity is uncharacterised\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism linking CGP-dependent PCR stabilisation to activation of gliding motility, and the structural basis of its interactions with FRM1 and ASAF1, remain open.\",\n      \"evidence\": \"No further mechanistic evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of CGP within the PCR\",\n        \"No mapping of CGP binding interfaces to FRM1 or ASAF1\",\n        \"Mechanistic coupling of PCR integrity to motility activation not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0005198\",\n        \"supporting_discovery_ids\": [\n          1\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0020009\",\n        \"supporting_discovery_ids\": [\n          0,\n          1\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0071693\",\n        \"supporting_discovery_ids\": [\n          0\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"Preconoidal ring (PCR) / conoid complex\"\n    ],\n    \"partners\": [\n      \"FRM1\",\n      \"ASAF1\"\n    ],\n    \"other_free_text\": [\n      \"CGP stabilises preconoidal rings after replication but is dispensable for initial PCR assembly in daughter cells [#1]\",\n      \"CGP is required for activation of gliding motility during late egress [#0]\",\n      \"ASAF1 depletion abolishes conoid complex assembly, disorganises microtubules, and blocks daughter cell formation [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_240380","name":"CGP","product":"conoid gliding protein CGP","uniprot_acc":"S8F7I2","chromosome":"TGME49_chrVI","start_pos":1215953},{"strain":"GT1","gene_id":"TGGT1_240380","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVI","start_pos":1188384},{"strain":"RH88","gene_id":"TGRH88_030760","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023087","start_pos":2470116},{"strain":"VEG","gene_id":"TGVEG_240380","name":null,"product":"translation initiation factor eIF3 subunit 135","uniprot_acc":"B9QK58","chromosome":"TGVEG_chrVI","start_pos":1232725}]}