{"gene":"TG_263180","gene_symbol":"MyoD","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2006,"finding":"TgMyoD (class XIV myosin) exhibits similar transient kinetic properties to TgMyoA in in vitro biophysical assays, indicating comparable motor activity. Despite this, genetic disruption of the TgMyoD gene by double homologous recombination showed it is dispensable for tachyzoite gliding motility, host cell invasion, egress, and virulence in mice. TgMyoD is predominantly expressed in bradyzoites, explaining the absence of tachyzoite phenotype and suggesting a role restricted to the cyst-forming stage.","method":"Transient kinetic assays (in vitro biophysical analysis), double homologous recombination gene disruption, gliding motility assays, mouse virulence assays, stage-specific expression analysis","journal":"Journal of muscle research and cell motility","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro enzymatic kinetic analysis combined with clean gene knockout and multiple functional readouts (motility, invasion, virulence) in a single rigorous study","pmids":["16470333"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2011,"finding":"MLC2 associates with TgMyoD via its calmodulin-like domain and is anchored to the plasma membrane of T. gondii via its N-terminal extension, likely through palmitoylation. This defines an unusual MyoD-MLC2 motor complex anchored at the plasma membrane, distinct from the inner membrane complex localization of MyoA-MLC1.","method":"Subcellular localization (immunofluorescence/fractionation), molecular modeling, identification of MLC2 as MyoD-associated light chain via co-localization and interaction studies","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — direct localization and interaction data from a single lab using multiple approaches (modeling, localization, palmitoylation inference), but full reconstitution/mutagenesis not described in abstract","pmids":["21143563"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"TgMyoD is a class XIV myosin with kinetic properties similar to TgMyoA; it forms a complex with the light chain MLC2 (via MLC2's calmodulin-like domain) that is anchored to the plasma membrane likely via palmitoylation, is dispensable for tachyzoite motility and virulence, and is predominantly expressed in bradyzoites suggesting a motor function specific to the cyst-forming stage."},"narrative":{"mechanistic_narrative":"TgMyoD is a class XIV myosin of Toxoplasma gondii that possesses in vitro motor activity kinetically comparable to the glideosome motor TgMyoA, yet is functionally distinct in its cellular role [PMID:16470333]. Genetic disruption demonstrates it is dispensable for tachyzoite gliding motility, host cell invasion, egress, and virulence, a lack of phenotype explained by its predominant expression in bradyzoites, which points to a motor function restricted to the cyst-forming stage [PMID:16470333]. TgMyoD forms a complex with the light chain MLC2, which binds via its calmodulin-like domain and anchors the motor to the plasma membrane through an N-terminal extension likely modified by palmitoylation — a localization distinct from the inner membrane complex positioning of the MyoA-MLC1 motor [PMID:21143563]. Beyond this motor-light chain complex and its stage-restricted expression, no further mechanistic detail on TgMyoD's cellular function has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Whether TgMyoD is a functional motor and whether it contributes to the actinomyosin-driven motility that powers tachyzoite invasion was unknown; kinetic and knockout analysis established that it is a bona fide motor yet dispensable for the tachyzoite lytic cycle.","evidence":"Transient kinetic biophysical assays plus double homologous recombination knockout scored for gliding, invasion, egress, and mouse virulence, with stage-specific expression analysis","pmids":["16470333"],"confidence":"High","gaps":["The specific cargo, track, or cellular process TgMyoD drives in bradyzoites was not identified","No bradyzoite-stage functional assay directly tested a phenotype for TgMyoD","The structural basis of its motor activity was not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2011,"claim":"The light chain partner and subcellular positioning of the TgMyoD motor were undefined; identifying MLC2 and mapping its plasma-membrane anchoring established a MyoD-MLC2 complex distinct from the IMC-localized MyoA-MLC1 glideosome.","evidence":"Subcellular localization by immunofluorescence/fractionation, molecular modeling, and identification of MLC2 as the MyoD-associated light chain via co-localization and interaction studies","pmids":["21143563"],"confidence":"Medium","gaps":["Full reconstitution and mutagenesis of the MyoD-MLC2 interface were not described","Palmitoylation of the MLC2 N-terminal extension was inferred rather than directly demonstrated","Functional consequence of plasma-membrane anchoring for the motor was not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The physiological substrate and cellular role of the plasma-membrane-anchored MyoD-MLC2 motor within the cyst-forming bradyzoite stage remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No bradyzoite-specific function has been assigned to TgMyoD","The cargo moved and the biological process served by plasma-membrane anchoring are unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["MyoD-MLC2 plasma-membrane-anchored motor complex"],"partners":["MLC2 (MYOSIN LIGHT CHAIN, BINDS VIA CALMODULIN-LIKE DOMAIN)"],"other_free_text":["Class XIV myosin with transient kinetic properties similar to TgMyoA [#0]","Dispensable for tachyzoite gliding motility, invasion, egress, and mouse virulence [#0]","Predominantly expressed in bradyzoites, suggesting a cyst-stage-specific role [#0]","MLC2 anchored to plasma membrane via N-terminal extension, likely palmitoylation-dependent [#1]","MyoD-MLC2 complex localization is distinct from the IMC-localized MyoA-MLC1 glideosome [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"19097936","id":"PMC_19097936","title":"Primary skeletal muscle cells trigger spontaneous Toxoplasma gondii tachyzoite-to-bradyzoite conversion at higher rates than fibroblasts.","date":"2008","source":"International journal of medical microbiology : IJMM","url":"https://pubmed.ncbi.nlm.nih.gov/19097936","citation_count":58,"is_preprint":false},{"pmid":"21143563","id":"PMC_21143563","title":"Unusual anchor of a motor complex (MyoD-MLC2) to the plasma membrane of Toxoplasma gondii.","date":"2011","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/21143563","citation_count":28,"is_preprint":false},{"pmid":"16470333","id":"PMC_16470333","title":"Functional and biophysical analyses of the class XIV Toxoplasma gondii myosin D.","date":"2006","source":"Journal of muscle research and cell motility","url":"https://pubmed.ncbi.nlm.nih.gov/16470333","citation_count":14,"is_preprint":false},{"pmid":"31828046","id":"PMC_31828046","title":"Toxoplasma gondii Impairs Myogenesis in vitro, With Changes in Myogenic Regulatory Factors, Altered Host Cell Proliferation and Secretory Profile.","date":"2019","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31828046","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4338,"output_tokens":769,"usd":0.012275,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5550,"output_tokens":1874,"usd":0.0373,"stage2_stop_reason":"end_turn"},"total_usd":0.049575,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"TgMyoD (class XIV myosin) exhibits similar transient kinetic properties to TgMyoA in in vitro biophysical assays, indicating comparable motor activity. Despite this, genetic disruption of the TgMyoD gene by double homologous recombination showed it is dispensable for tachyzoite gliding motility, host cell invasion, egress, and virulence in mice. TgMyoD is predominantly expressed in bradyzoites, explaining the absence of tachyzoite phenotype and suggesting a role restricted to the cyst-forming stage.\",\n      \"method\": \"Transient kinetic assays (in vitro biophysical analysis), double homologous recombination gene disruption, gliding motility assays, mouse virulence assays, stage-specific expression analysis\",\n      \"journal\": \"Journal of muscle research and cell motility\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro enzymatic kinetic analysis combined with clean gene knockout and multiple functional readouts (motility, invasion, virulence) in a single rigorous study\",\n      \"pmids\": [\"16470333\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"MLC2 associates with TgMyoD via its calmodulin-like domain and is anchored to the plasma membrane of T. gondii via its N-terminal extension, likely through palmitoylation. This defines an unusual MyoD-MLC2 motor complex anchored at the plasma membrane, distinct from the inner membrane complex localization of MyoA-MLC1.\",\n      \"method\": \"Subcellular localization (immunofluorescence/fractionation), molecular modeling, identification of MLC2 as MyoD-associated light chain via co-localization and interaction studies\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — direct localization and interaction data from a single lab using multiple approaches (modeling, localization, palmitoylation inference), but full reconstitution/mutagenesis not described in abstract\",\n      \"pmids\": [\"21143563\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgMyoD is a class XIV myosin with kinetic properties similar to TgMyoA; it forms a complex with the light chain MLC2 (via MLC2's calmodulin-like domain) that is anchored to the plasma membrane likely via palmitoylation, is dispensable for tachyzoite motility and virulence, and is predominantly expressed in bradyzoites suggesting a motor function specific to the cyst-forming stage.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgMyoD is a class XIV myosin of Toxoplasma gondii that possesses in vitro motor activity kinetically comparable to the glideosome motor TgMyoA, yet is functionally distinct in its cellular role [#0]. Genetic disruption demonstrates it is dispensable for tachyzoite gliding motility, host cell invasion, egress, and virulence, a lack of phenotype explained by its predominant expression in bradyzoites, which points to a motor function restricted to the cyst-forming stage [#0]. TgMyoD forms a complex with the light chain MLC2, which binds via its calmodulin-like domain and anchors the motor to the plasma membrane through an N-terminal extension likely modified by palmitoylation — a localization distinct from the inner membrane complex positioning of the MyoA-MLC1 motor [#1]. Beyond this motor-light chain complex and its stage-restricted expression, no further mechanistic detail on TgMyoD's cellular function has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Whether TgMyoD is a functional motor and whether it contributes to the actinomyosin-driven motility that powers tachyzoite invasion was unknown; kinetic and knockout analysis established that it is a bona fide motor yet dispensable for the tachyzoite lytic cycle.\",\n      \"evidence\": \"Transient kinetic biophysical assays plus double homologous recombination knockout scored for gliding, invasion, egress, and mouse virulence, with stage-specific expression analysis\",\n      \"pmids\": [\"16470333\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The specific cargo, track, or cellular process TgMyoD drives in bradyzoites was not identified\",\n        \"No bradyzoite-stage functional assay directly tested a phenotype for TgMyoD\",\n        \"The structural basis of its motor activity was not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"The light chain partner and subcellular positioning of the TgMyoD motor were undefined; identifying MLC2 and mapping its plasma-membrane anchoring established a MyoD-MLC2 complex distinct from the IMC-localized MyoA-MLC1 glideosome.\",\n      \"evidence\": \"Subcellular localization by immunofluorescence/fractionation, molecular modeling, and identification of MLC2 as the MyoD-associated light chain via co-localization and interaction studies\",\n      \"pmids\": [\"21143563\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Full reconstitution and mutagenesis of the MyoD-MLC2 interface were not described\",\n        \"Palmitoylation of the MLC2 N-terminal extension was inferred rather than directly demonstrated\",\n        \"Functional consequence of plasma-membrane anchoring for the motor was not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological substrate and cellular role of the plasma-membrane-anchored MyoD-MLC2 motor within the cyst-forming bradyzoite stage remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No bradyzoite-specific function has been assigned to TgMyoD\",\n        \"The cargo moved and the biological process served by plasma-membrane anchoring are unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0000146\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"MyoD-MLC2 plasma-membrane-anchored motor complex\"],\n    \"partners\": [\"MLC2 (myosin light chain, binds via calmodulin-like domain)\"],\n    \"other_free_text\": [\n      \"Class XIV myosin with transient kinetic properties similar to TgMyoA [#0]\",\n      \"Dispensable for tachyzoite gliding motility, invasion, egress, and mouse virulence [#0]\",\n      \"Predominantly expressed in bradyzoites, suggesting a cyst-stage-specific role [#0]\",\n      \"MLC2 anchored to plasma membrane via N-terminal extension, likely palmitoylation-dependent [#1]\",\n      \"MyoD-MLC2 complex localization is distinct from the IMC-localized MyoA-MLC1 glideosome [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_263180","name":"MyoD","product":"myosin D","uniprot_acc":"A0A125YIS8","chromosome":"TGME49_chrVIIb","start_pos":738850},{"strain":"GT1","gene_id":"TGGT1_263180","name":null,"product":"myosin D","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":714013},{"strain":"RH88","gene_id":"TGRH88_067840","name":null,"product":"myosin D","uniprot_acc":null,"chromosome":"CM023089","start_pos":752271},{"strain":"VEG","gene_id":"TGVEG_263180","name":null,"product":"myosin D","uniprot_acc":"B6KC84","chromosome":"TGVEG_chrVIIb","start_pos":744733}]}