{"gene":"TG_232410","gene_symbol":"TRXL1","run_date":"2026-09-08T12:58:24","timeline":{"discoveries":[{"year":2013,"finding":"TrxL1 contains a thioredoxin-like fold and is a component of a protein complex that coats the cortical microtubules of Toxoplasma gondii. Despite its stable association with cortical microtubules, TrxL1 does not bind microtubules directly.","method":"Endogenous tagging with mEmeraldFP, structured illumination superresolution microscopy, coimmunoprecipitation","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and direct localization imaging, single lab, two orthogonal methods","pmids":["23873863"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"SPM1 recruits TrxL1 to the cortical microtubules, placing SPM1 upstream of TrxL1 in the assembly of the cortical microtubule-associated complex.","method":"Coimmunoprecipitation, fluorescence localization","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and localization data, single lab, two complementary approaches","pmids":["23873863"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"TrxL1 co-precipitates with a complex containing SPM1 and TrxL2 (a close homolog of TrxL1) as well as several other novel proteins, defining the composition of this cortical microtubule-coating complex.","method":"Coimmunoprecipitation followed by mass spectrometry (Florens lab involvement implies MS)","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP/MS for complex identification, single lab","pmids":["23873863"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"Cryo-EM ex vivo structure of Toxoplasma cortical microtubules identifies TrxL1, TrxL2, and SPM1 as bona fide microtubule inner proteins (MIPs) that form a mesh on the luminal surface and simultaneously stabilize the tubulin lattice in both longitudinal and lateral directions.","method":"Single-particle cryo-EM structure determination","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution cryo-EM structure with direct visualization of MIP positions and deletion phenotypes confirming MT stability role","pmids":["34031406"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"Deletion of TrxL1 (along with TrxL2 and SPM1) compromises microtubule stability and integrity under detergent and cold treatment challenges, demonstrating that TrxL1 is required for cortical microtubule stability.","method":"Gene deletion followed by chemical challenge assays (detergent/cold treatment)","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined cellular phenotype, corroborated by structural data in the same study and consistent with prior literature","pmids":["34031406"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TrxL1 is a thioredoxin-fold microtubule inner protein (MIP) that is recruited to the luminal surface of Toxoplasma gondii cortical microtubules by SPM1, where it forms a stabilizing mesh together with TrxL2 and SPM1 that reinforces the tubulin lattice in both longitudinal and lateral directions without directly binding microtubules itself, and its deletion compromises cortical microtubule stability."},"narrative":{"mechanistic_narrative":"TrxL1 is a thioredoxin-fold microtubule inner protein (MIP) that stabilizes the cortical microtubules of Toxoplasma gondii [PMID:23873863, PMID:34031406]. Although it associates stably with cortical microtubules, it does not bind them directly; instead it is recruited to the luminal microtubule surface by SPM1, which acts upstream in assembly of the cortical microtubule-coating complex [PMID:23873863]. Within this complex TrxL1 co-assembles with its homolog TrxL2 and with SPM1 [PMID:23873863], and cryo-EM shows the three proteins form a luminal mesh that simultaneously reinforces the tubulin lattice in longitudinal and lateral directions [PMID:34031406]. Deletion of TrxL1 compromises microtubule stability and integrity under detergent and cold challenge, establishing it as required for cortical microtubule stability [PMID:34031406]. Beyond this structural stabilizing role, no catalytic or redox activity for the thioredoxin-like fold has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Establishing that TrxL1 is a thioredoxin-fold protein stably coating cortical microtubules yet not binding them directly reframed how it must be tethered to the cytoskeleton.","evidence":"Endogenous mEmeraldFP tagging, superresolution imaging, and coimmunoprecipitation in T. gondii","pmids":["23873863"],"confidence":"Medium","gaps":["No demonstration of any redox or catalytic function for the thioredoxin fold","Mechanism of indirect microtubule association not defined at this stage"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"claim":"Identifying SPM1 as the recruiter of TrxL1 and defining the SPM1/TrxL2/TrxL1 complex composition resolved the assembly hierarchy of the microtubule-coating complex.","evidence":"Coimmunoprecipitation, mass spectrometry, and fluorescence localization in T. gondii","pmids":["23873863"],"confidence":"Medium","gaps":["Single-lab Co-IP/MS without reciprocal validation for all partners","Functional consequence of the complex on microtubules not yet tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"Cryo-EM structural determination redefined TrxL1 as a bona fide microtubule inner protein forming a luminal mesh that stabilizes the tubulin lattice, explaining its indirect association observed earlier.","evidence":"Single-particle cryo-EM of ex vivo cortical microtubules from T. gondii","pmids":["34031406"],"confidence":"High","gaps":["Contribution of the thioredoxin fold to lattice reinforcement versus a scaffolding role not dissected","Whether TrxL1 has any redox chemistry within the lumen unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"Gene deletion demonstrated that TrxL1 is functionally required for cortical microtubule stability, converting the structural picture into a defined cellular role.","evidence":"Gene deletion with detergent and cold challenge assays in T. gondii","pmids":["34031406"],"confidence":"High","gaps":["Individual contribution of TrxL1 versus TrxL2 and SPM1 to the phenotype not fully separated","Downstream effects on parasite motility, invasion, or replication not quantified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"Whether the thioredoxin-like fold of TrxL1 carries any redox or enzymatic activity, or is purely a structural scaffold, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No biochemical test of thioredoxin catalytic activity in the corpus","No identified substrate or redox partner"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Cortical microtubule-coating complex (TrxL1, TrxL2, SPM1, and additional novel proteins)"],"partners":["SPM1 (RECRUITER, UPSTREAM IN ASSEMBLY)","TRXL2 (CLOSE HOMOLOG, CO-COMPLEX MEMBER)"],"other_free_text":["TrxL1 is a microtubule inner protein (MIP) forming a luminal mesh that reinforces the tubulin lattice longitudinally and laterally without directly binding microtubules.","Thioredoxin-like fold present, but no redox or catalytic activity characterized in the available corpus."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"34031406","id":"PMC_34031406","title":"Cryo-EM structure of cortical microtubules from human parasite Toxoplasma gondii identifies their microtubule inner proteins.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34031406","citation_count":64,"is_preprint":false},{"pmid":"23873863","id":"PMC_23873863","title":"Novel thioredoxin-like proteins are components of a protein complex coating the cortical microtubules of Toxoplasma gondii.","date":"2013","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/23873863","citation_count":48,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3387,"output_tokens":1203,"usd":0.014103,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6160,"output_tokens":2057,"usd":0.041113,"stage2_stop_reason":"end_turn"},"total_usd":0.055216,"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\": 2013,\n      \"finding\": \"TrxL1 contains a thioredoxin-like fold and is a component of a protein complex that coats the cortical microtubules of Toxoplasma gondii. Despite its stable association with cortical microtubules, TrxL1 does not bind microtubules directly.\",\n      \"method\": \"Endogenous tagging with mEmeraldFP, structured illumination superresolution microscopy, coimmunoprecipitation\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and direct localization imaging, single lab, two orthogonal methods\",\n      \"pmids\": [\"23873863\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"SPM1 recruits TrxL1 to the cortical microtubules, placing SPM1 upstream of TrxL1 in the assembly of the cortical microtubule-associated complex.\",\n      \"method\": \"Coimmunoprecipitation, fluorescence localization\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and localization data, single lab, two complementary approaches\",\n      \"pmids\": [\"23873863\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TrxL1 co-precipitates with a complex containing SPM1 and TrxL2 (a close homolog of TrxL1) as well as several other novel proteins, defining the composition of this cortical microtubule-coating complex.\",\n      \"method\": \"Coimmunoprecipitation followed by mass spectrometry (Florens lab involvement implies MS)\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP/MS for complex identification, single lab\",\n      \"pmids\": [\"23873863\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Cryo-EM ex vivo structure of Toxoplasma cortical microtubules identifies TrxL1, TrxL2, and SPM1 as bona fide microtubule inner proteins (MIPs) that form a mesh on the luminal surface and simultaneously stabilize the tubulin lattice in both longitudinal and lateral directions.\",\n      \"method\": \"Single-particle cryo-EM structure determination\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution cryo-EM structure with direct visualization of MIP positions and deletion phenotypes confirming MT stability role\",\n      \"pmids\": [\"34031406\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Deletion of TrxL1 (along with TrxL2 and SPM1) compromises microtubule stability and integrity under detergent and cold treatment challenges, demonstrating that TrxL1 is required for cortical microtubule stability.\",\n      \"method\": \"Gene deletion followed by chemical challenge assays (detergent/cold treatment)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined cellular phenotype, corroborated by structural data in the same study and consistent with prior literature\",\n      \"pmids\": [\"34031406\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TrxL1 is a thioredoxin-fold microtubule inner protein (MIP) that is recruited to the luminal surface of Toxoplasma gondii cortical microtubules by SPM1, where it forms a stabilizing mesh together with TrxL2 and SPM1 that reinforces the tubulin lattice in both longitudinal and lateral directions without directly binding microtubules itself, and its deletion compromises cortical microtubule stability.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TrxL1 is a thioredoxin-fold microtubule inner protein (MIP) that stabilizes the cortical microtubules of Toxoplasma gondii [#0, #3]. Although it associates stably with cortical microtubules, it does not bind them directly; instead it is recruited to the luminal microtubule surface by SPM1, which acts upstream in assembly of the cortical microtubule-coating complex [#0, #1]. Within this complex TrxL1 co-assembles with its homolog TrxL2 and with SPM1 [#2], and cryo-EM shows the three proteins form a luminal mesh that simultaneously reinforces the tubulin lattice in longitudinal and lateral directions [#3]. Deletion of TrxL1 compromises microtubule stability and integrity under detergent and cold challenge, establishing it as required for cortical microtubule stability [#4]. Beyond this structural stabilizing role, no catalytic or redox activity for the thioredoxin-like fold has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing that TrxL1 is a thioredoxin-fold protein stably coating cortical microtubules yet not binding them directly reframed how it must be tethered to the cytoskeleton.\",\n      \"evidence\": \"Endogenous mEmeraldFP tagging, superresolution imaging, and coimmunoprecipitation in T. gondii\",\n      \"pmids\": [\"23873863\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No demonstration of any redox or catalytic function for the thioredoxin fold\", \"Mechanism of indirect microtubule association not defined at this stage\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identifying SPM1 as the recruiter of TrxL1 and defining the SPM1/TrxL2/TrxL1 complex composition resolved the assembly hierarchy of the microtubule-coating complex.\",\n      \"evidence\": \"Coimmunoprecipitation, mass spectrometry, and fluorescence localization in T. gondii\",\n      \"pmids\": [\"23873863\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab Co-IP/MS without reciprocal validation for all partners\", \"Functional consequence of the complex on microtubules not yet tested\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Cryo-EM structural determination redefined TrxL1 as a bona fide microtubule inner protein forming a luminal mesh that stabilizes the tubulin lattice, explaining its indirect association observed earlier.\",\n      \"evidence\": \"Single-particle cryo-EM of ex vivo cortical microtubules from T. gondii\",\n      \"pmids\": [\"34031406\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Contribution of the thioredoxin fold to lattice reinforcement versus a scaffolding role not dissected\", \"Whether TrxL1 has any redox chemistry within the lumen unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Gene deletion demonstrated that TrxL1 is functionally required for cortical microtubule stability, converting the structural picture into a defined cellular role.\",\n      \"evidence\": \"Gene deletion with detergent and cold challenge assays in T. gondii\",\n      \"pmids\": [\"34031406\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Individual contribution of TrxL1 versus TrxL2 and SPM1 to the phenotype not fully separated\", \"Downstream effects on parasite motility, invasion, or replication not quantified\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the thioredoxin-like fold of TrxL1 carries any redox or enzymatic activity, or is purely a structural scaffold, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No biochemical test of thioredoxin catalytic activity in the corpus\", \"No identified substrate or redox partner\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008017\", \"supporting_discovery_ids\": [3, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005881\", \"supporting_discovery_ids\": [0, 1, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0043622\", \"supporting_discovery_ids\": [4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"Cortical microtubule-coating complex (TrxL1, TrxL2, SPM1, and additional novel proteins)\"\n    ],\n    \"partners\": [\n      \"SPM1 (recruiter, upstream in assembly)\",\n      \"TrxL2 (close homolog, co-complex member)\"\n    ],\n    \"other_free_text\": [\n      \"TrxL1 is a microtubule inner protein (MIP) forming a luminal mesh that reinforces the tubulin lattice longitudinally and laterally without directly binding microtubules.\",\n      \"Thioredoxin-like fold present, but no redox or catalytic activity characterized in the available corpus.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_232410","name":"TRXL1","product":"thioredoxin-like protein 1","uniprot_acc":"A0A125YMM3","chromosome":"TGME49_chrVIII","start_pos":2078643},{"strain":"GT1","gene_id":"TGGT1_232410","name":null,"product":"PDI family protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":2074655},{"strain":"RH88","gene_id":"TGRH88_076520","name":null,"product":"PDI family protein","uniprot_acc":null,"chromosome":"CM023089","start_pos":7184929},{"strain":"VEG","gene_id":"TGVEG_232410","name":null,"product":"PDI family protein","uniprot_acc":"A0A0F7UXJ4","chromosome":"TGVEG_chrVIII","start_pos":2087641}]}