{"gene":"TG_294860","gene_symbol":"BCC0","run_date":"2026-09-08T18:09:50+00:00","timeline":{"discoveries":[{"year":2022,"finding":"BCC0 is a basal complex (BC) protein that undergirds BC formation, appearing in five foci that precede the symmetry seen in the apical annuli and IMC sutures during daughter budding; daughter budding from BCC0 foci progresses bidirectionally—apical cap forms in the apical direction and the rest of the IMC in the basal direction.","method":"Reciprocal proximity-based biotinylation (BioID) proteome mapping combined with disruption of component expression and spatiotemporal imaging","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal BioID proximity labeling plus functional disruption assays in a single lab with multiple orthogonal approaches","pmids":["35941170"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"BCC0 is an essential, early-recruiting IMC protein that forms a trimeric daughter bud assembly complex with IMC32 and IMC43; BCC0 localization to daughter buds depends on the presence of both IMC32 and IMC43.","method":"Proximity labeling (BioID) using IMC32 as bait, yeast two-hybrid screen, and conditional/genetic knockdown with localization assays","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal proximity labeling, yeast two-hybrid, deletion analyses, and functional complementation studies all converging on the same conclusion in a single rigorous study","pmids":["39024411"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"Residues 701–877 of BCC0 constitute an essential domain required for both its localization and function; residues 1–899 are sufficient for function despite minor mislocalization.","method":"Deletion analyses and functional complementation studies","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — deletion mapping combined with functional complementation in a single lab","pmids":["39024411"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"BCC0's essential domain (residues 701–877) directly binds the coiled-coil region of IMC32, whereas BCC0 and IMC43 do not directly interact, supporting a model in which an IMC32–BCC0 subcomplex initially recruits to nascent buds via palmitoylation of IMC32 and is locked into the scaffold upon bud elongation when IMC32 binds IMC43.","method":"Pairwise yeast two-hybrid assays","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid pairwise interaction mapping with domain-level resolution, single lab","pmids":["39024411"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"BCC0 is an essential, early-recruiting inner membrane complex (IMC) protein in Toxoplasma gondii that forms a trimeric daughter bud assembly complex with IMC32 and IMC43: it is recruited to nascent daughter buds via direct binding of its essential domain (residues 701–877) to the coiled-coil region of IMC32 (itself anchored by palmitoylation), depends on both IMC32 and IMC43 for proper localization, and undergirds basal complex formation by appearing as five foci from which daughter budding proceeds bidirectionally to template assembly of the entire IMC scaffold during endodyogeny."},"narrative":{"mechanistic_narrative":"BCC0 is an essential inner membrane complex (IMC) protein of Toxoplasma gondii that seeds daughter cell construction during endodyogeny by nucleating the basal complex and templating IMC scaffold assembly [PMID:35941170, PMID:39024411]. It first appears as five foci that precede the symmetry of the apical annuli and IMC sutures; daughter budding proceeds bidirectionally from these foci, with the apical cap forming apically and the remainder of the IMC forming basally [PMID:35941170]. Mechanistically, BCC0 is an early-recruiting component of a trimeric daughter bud assembly complex with IMC32 and IMC43, and its recruitment to nascent buds requires the presence of both partners [PMID:39024411]. Recruitment is driven by direct binding of its essential C-terminal domain (residues 701–877) to the coiled-coil region of IMC32, while BCC0 and IMC43 do not interact directly; this supports a model in which a palmitoylation-anchored IMC32–BCC0 subcomplex is recruited to nascent buds and locked into the scaffold once IMC32 engages IMC43 during bud elongation [PMID:39024411].","teleology":[{"year":2022,"claim":"Before this work it was unknown which proteins organize basal complex formation and how daughter budding is spatially initiated; identifying BCC0 as a basal complex protein appearing in five foci that precede IMC suture symmetry established it as an early spatial organizer of the daughter bud.","evidence":"Reciprocal BioID proximity proteomics with expression disruption and spatiotemporal imaging in T. gondii","pmids":["35941170"],"confidence":"Medium","gaps":["Direct binding partners of BCC0 not yet identified","Molecular basis of the five-foci patterning unresolved","Whether BCC0 is required for viability not established here"],"attribution":[]},{"year":2024,"claim":"It was unclear whether BCC0 acts alone or within a defined assembly module; showing it forms a trimeric complex with IMC32 and IMC43 and requires both for daughter-bud localization established BCC0 as an essential, dependency-constrained node of an early IMC assembly complex.","evidence":"IMC32-bait BioID, yeast two-hybrid screening, and conditional knockdown with localization assays in T. gondii","pmids":["39024411"],"confidence":"High","gaps":["Structural architecture of the trimeric complex not determined","Order-of-assembly kinetics in vivo not directly measured"],"attribution":[]},{"year":2024,"claim":"The functional region of BCC0 was undefined; deletion mapping localized an essential domain to residues 701–877 required for both localization and function, with residues 1–899 sufficient for function, defining the minimal functional unit.","evidence":"Deletion analyses and functional complementation in T. gondii","pmids":["39024411"],"confidence":"Medium","gaps":["Role of the N-terminal region outside the essential domain not defined","Structural fold of residues 701–877 unknown"],"attribution":[]},{"year":2024,"claim":"The physical basis of BCC0 recruitment was unknown; pairwise interaction mapping showed its essential domain binds the IMC32 coiled-coil directly while BCC0 does not contact IMC43, yielding a stepwise recruitment model in which a palmitoylation-anchored IMC32–BCC0 subcomplex is locked into the scaffold upon IMC32–IMC43 binding.","evidence":"Pairwise yeast two-hybrid interaction assays in T. gondii","pmids":["39024411"],"confidence":"Medium","gaps":["Direct interaction not confirmed in native cellular context beyond Y2H","Timing of the IMC32–IMC43 lock-in step not directly visualized","Whether additional factors stabilize the subcomplex unknown"],"attribution":[]},{"year":null,"claim":"How the five BCC0 foci are positioned and how bidirectional IMC templating is mechanistically driven from them remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the BCC0–IMC32–IMC43 complex","Upstream determinants of five-foci patterning unknown","Molecular link between BCC0 and bidirectional bud elongation not established"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Trimeric daughter bud assembly complex (BCC0–IMC32–IMC43)"],"partners":["IMC32 (DIRECT, VIA BCC0 RESIDUES 701–877 BINDING THE IMC32 COILED-COIL)","IMC43 (INDIRECT; NO DIRECT BCC0–IMC43 INTERACTION)"],"other_free_text":["BCC0 is an essential, early-recruiting IMC/basal complex protein in Toxoplasma gondii.","Essential domain mapped to residues 701–877; residues 1–899 sufficient for function.","Appears as five foci that seed bidirectional daughter budding during endodyogeny.","Recruitment to daughter buds depends on both IMC32 and IMC43."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"35941170","id":"PMC_35941170","title":"Proteomic characterization of the Toxoplasma gondii cytokinesis machinery portrays an expanded hierarchy of its assembly and function.","date":"2022","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/35941170","citation_count":46,"is_preprint":false},{"pmid":"39024411","id":"PMC_39024411","title":"BCC0 collaborates with IMC32 and IMC43 to form the Toxoplasma gondii essential daughter bud assembly complex.","date":"2024","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/39024411","citation_count":7,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3283,"output_tokens":1090,"usd":0.0131,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6039,"output_tokens":2160,"usd":0.042098,"stage2_stop_reason":"end_turn"},"total_usd":0.0,"stage1_batch_id":"msgbatch_01WgHz6kceqm573AGLyz57at","stage2_batch_id":"msgbatch_01LK4wDYj5zYquahv7gi9893","note":"batch pricing = 50% of standard","skipped":true},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"BCC0 is a basal complex (BC) protein that undergirds BC formation, appearing in five foci that precede the symmetry seen in the apical annuli and IMC sutures during daughter budding; daughter budding from BCC0 foci progresses bidirectionally—apical cap forms in the apical direction and the rest of the IMC in the basal direction.\",\n      \"method\": \"Reciprocal proximity-based biotinylation (BioID) proteome mapping combined with disruption of component expression and spatiotemporal imaging\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal BioID proximity labeling plus functional disruption assays in a single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"35941170\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"BCC0 is an essential, early-recruiting IMC protein that forms a trimeric daughter bud assembly complex with IMC32 and IMC43; BCC0 localization to daughter buds depends on the presence of both IMC32 and IMC43.\",\n      \"method\": \"Proximity labeling (BioID) using IMC32 as bait, yeast two-hybrid screen, and conditional/genetic knockdown with localization assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal proximity labeling, yeast two-hybrid, deletion analyses, and functional complementation studies all converging on the same conclusion in a single rigorous study\",\n      \"pmids\": [\"39024411\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Residues 701–877 of BCC0 constitute an essential domain required for both its localization and function; residues 1–899 are sufficient for function despite minor mislocalization.\",\n      \"method\": \"Deletion analyses and functional complementation studies\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — deletion mapping combined with functional complementation in a single lab\",\n      \"pmids\": [\"39024411\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"BCC0's essential domain (residues 701–877) directly binds the coiled-coil region of IMC32, whereas BCC0 and IMC43 do not directly interact, supporting a model in which an IMC32–BCC0 subcomplex initially recruits to nascent buds via palmitoylation of IMC32 and is locked into the scaffold upon bud elongation when IMC32 binds IMC43.\",\n      \"method\": \"Pairwise yeast two-hybrid assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid pairwise interaction mapping with domain-level resolution, single lab\",\n      \"pmids\": [\"39024411\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"BCC0 is an essential, early-recruiting inner membrane complex (IMC) protein in Toxoplasma gondii that forms a trimeric daughter bud assembly complex with IMC32 and IMC43: it is recruited to nascent daughter buds via direct binding of its essential domain (residues 701–877) to the coiled-coil region of IMC32 (itself anchored by palmitoylation), depends on both IMC32 and IMC43 for proper localization, and undergirds basal complex formation by appearing as five foci from which daughter budding proceeds bidirectionally to template assembly of the entire IMC scaffold during endodyogeny.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"BCC0 is an essential inner membrane complex (IMC) protein of Toxoplasma gondii that seeds daughter cell construction during endodyogeny by nucleating the basal complex and templating IMC scaffold assembly [#0, #1]. It first appears as five foci that precede the symmetry of the apical annuli and IMC sutures; daughter budding proceeds bidirectionally from these foci, with the apical cap forming apically and the remainder of the IMC forming basally [#0]. Mechanistically, BCC0 is an early-recruiting component of a trimeric daughter bud assembly complex with IMC32 and IMC43, and its recruitment to nascent buds requires the presence of both partners [#1]. Recruitment is driven by direct binding of its essential C-terminal domain (residues 701\\u2013877) to the coiled-coil region of IMC32, while BCC0 and IMC43 do not interact directly; this supports a model in which a palmitoylation-anchored IMC32\\u2013BCC0 subcomplex is recruited to nascent buds and locked into the scaffold once IMC32 engages IMC43 during bud elongation [#2, #3].\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Before this work it was unknown which proteins organize basal complex formation and how daughter budding is spatially initiated; identifying BCC0 as a basal complex protein appearing in five foci that precede IMC suture symmetry established it as an early spatial organizer of the daughter bud.\",\n      \"evidence\": \"Reciprocal BioID proximity proteomics with expression disruption and spatiotemporal imaging in T. gondii\",\n      \"pmids\": [\"35941170\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding partners of BCC0 not yet identified\", \"Molecular basis of the five-foci patterning unresolved\", \"Whether BCC0 is required for viability not established here\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unclear whether BCC0 acts alone or within a defined assembly module; showing it forms a trimeric complex with IMC32 and IMC43 and requires both for daughter-bud localization established BCC0 as an essential, dependency-constrained node of an early IMC assembly complex.\",\n      \"evidence\": \"IMC32-bait BioID, yeast two-hybrid screening, and conditional knockdown with localization assays in T. gondii\",\n      \"pmids\": [\"39024411\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural architecture of the trimeric complex not determined\", \"Order-of-assembly kinetics in vivo not directly measured\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The functional region of BCC0 was undefined; deletion mapping localized an essential domain to residues 701\\u2013877 required for both localization and function, with residues 1\\u2013899 sufficient for function, defining the minimal functional unit.\",\n      \"evidence\": \"Deletion analyses and functional complementation in T. gondii\",\n      \"pmids\": [\"39024411\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Role of the N-terminal region outside the essential domain not defined\", \"Structural fold of residues 701\\u2013877 unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The physical basis of BCC0 recruitment was unknown; pairwise interaction mapping showed its essential domain binds the IMC32 coiled-coil directly while BCC0 does not contact IMC43, yielding a stepwise recruitment model in which a palmitoylation-anchored IMC32\\u2013BCC0 subcomplex is locked into the scaffold upon IMC32\\u2013IMC43 binding.\",\n      \"evidence\": \"Pairwise yeast two-hybrid interaction assays in T. gondii\",\n      \"pmids\": [\"39024411\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct interaction not confirmed in native cellular context beyond Y2H\", \"Timing of the IMC32\\u2013IMC43 lock-in step not directly visualized\", \"Whether additional factors stabilize the subcomplex unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the five BCC0 foci are positioned and how bidirectional IMC templating is mechanistically driven from them remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the BCC0\\u2013IMC32\\u2013IMC43 complex\", \"Upstream determinants of five-foci patterning unknown\", \"Molecular link between BCC0 and bidirectional bud elongation not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [1, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0061640\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Trimeric daughter bud assembly complex (BCC0\\u2013IMC32\\u2013IMC43)\"],\n    \"partners\": [\"IMC32 (direct, via BCC0 residues 701\\u2013877 binding the IMC32 coiled-coil)\", \"IMC43 (indirect; no direct BCC0\\u2013IMC43 interaction)\"],\n    \"other_free_text\": [\n      \"BCC0 is an essential, early-recruiting IMC/basal complex protein in Toxoplasma gondii.\",\n      \"Essential domain mapped to residues 701\\u2013877; residues 1\\u2013899 sufficient for function.\",\n      \"Appears as five foci that seed bidirectional daughter budding during endodyogeny.\",\n      \"Recruitment to daughter buds depends on both IMC32 and IMC43.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_294860","name":"BCC0","product":"basal complex component BCC0","uniprot_acc":"A0A125YFV2","chromosome":"TGME49_chrIa","start_pos":1221346},{"strain":"GT1","gene_id":"TGGT1_294860","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrIa","start_pos":1207560},{"strain":"RH88","gene_id":"TGRH88_019910","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023081","start_pos":1227154},{"strain":"VEG","gene_id":"TGVEG_294860","name":null,"product":"hypothetical protein","uniprot_acc":"B9PYE9","chromosome":"TGVEG_chrIa","start_pos":1230476}]}