{"gene":"TG_201220","gene_symbol":"PCR4","run_date":"2026-09-07T10:25:42","timeline":{"discoveries":[{"year":2022,"finding":"Pcr4 and Pcr5, which contain B-box zinc-finger domains, assemble as a heterodimer and are essential for the formation of the preconoidal rings (PCRs) in Toxoplasma gondii.","method":"Ultrastructure expansion microscopy, genetic loss-of-function (essentiality screens), protein interaction/assembly analysis","journal":"Nature microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct imaging with ultrastructure expansion microscopy plus loss-of-function demonstrating essentiality, multiple orthogonal methods in a single rigorous study","pmids":["36109645"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"The preconoidal rings (PCRs), whose formation requires Pcr4, serve as a hub for glideosome components including Formin1, linking the PCR structure to actomyosin-based gliding motility.","method":"Ultrastructure expansion microscopy, co-localization of glideosome components at the PCR hub","journal":"Nature microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ultrastructure expansion microscopy with functional co-localization data, multiple orthogonal methods in one rigorous study","pmids":["36109645"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Pcr4 and Pcr5 are conserved components of the preconoidal rings across Apicomplexa, indicating the heterodimeric B-box zinc-finger complex is a conserved structural element of the PCR in this phylum.","method":"Comparative genomics/sequence analysis combined with experimental localization and functional studies in Toxoplasma gondii","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — conservation inferred from sequence analysis plus experimental validation in Toxoplasma; cross-organism conservation not directly tested by reconstitution in other species","pmids":["36109645"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"Pcr4 contains a B-box zinc-finger domain, forms an essential heterodimer with Pcr5 to build the preconoidal rings (PCRs), and these rings serve as an assembly hub for glideosome components (including Formin1), thereby linking conoid architecture to actomyosin-driven motility and invasion in Toxoplasma gondii."},"narrative":{"mechanistic_narrative":"Pcr4 is a B-box zinc-finger protein that functions as an essential structural component of the preconoidal rings (PCRs) at the apical conoid of Toxoplasma gondii [PMID:36109645]. It assembles into a heterodimer with Pcr5, and this complex is required for PCR formation [PMID:36109645]. The PCRs built through Pcr4 serve as an assembly hub for glideosome components, including Formin1, thereby physically linking conoid architecture to the actomyosin machinery that drives gliding motility [PMID:36109645]. Pcr4 and its partner Pcr5 are conserved across Apicomplexa, indicating the heterodimeric B-box complex is a conserved structural element of the PCR in this phylum [PMID:36109645]. Beyond its role in PCR assembly and glideosome recruitment [PMID:36109645], no further biochemical or structural mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"Establishing what builds the preconoidal rings and whether specific proteins are essential answered a fundamental question about conoid architecture, identifying Pcr4 as a B-box zinc-finger protein that heterodimerizes with Pcr5 to form the PCRs.","evidence":"Ultrastructure expansion microscopy with genetic loss-of-function/essentiality analysis and protein assembly studies in Toxoplasma gondii","pmids":["36109645"],"confidence":"High","gaps":["No structural model of the Pcr4-Pcr5 heterodimer or the ring assembly is resolved","The role of the B-box zinc-finger domain in mediating heterodimerization is not dissected","How the heterodimer nucleates or is recruited to the preconoidal site is unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Determining how the conoid structure connects to motility showed that the Pcr4-dependent PCRs act as a hub recruiting glideosome components including Formin1, linking the apical structure to actomyosin-based gliding.","evidence":"Ultrastructure expansion microscopy with co-localization of glideosome components at the PCR hub in Toxoplasma gondii","pmids":["36109645"],"confidence":"High","gaps":["Direct physical interaction between Pcr4 and Formin1 is not demonstrated","The mechanistic contribution of the PCR to actin nucleation or motility output is not quantified","Whether loss of Pcr4 abolishes motility through loss of glideosome recruitment specifically is not isolated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Assessing evolutionary breadth indicated that the Pcr4-Pcr5 heterodimeric B-box complex is a conserved structural element of the PCR across Apicomplexa.","evidence":"Comparative genomics/sequence analysis with experimental localization and functional validation in Toxoplasma gondii","pmids":["36109645"],"confidence":"Medium","gaps":["Conservation is inferred from sequence analysis and not directly tested by reconstitution or functional assay in other apicomplexan species","Whether orthologs perform identical PCR and glideosome-hub functions in other species is untested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical basis of Pcr4 function — how its B-box domain drives heterodimerization, the atomic structure of the PCR, and the direct molecular links to specific glideosome proteins — remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural or biophysical characterization of the Pcr4-Pcr5 complex","No direct binding data between Pcr4 and glideosome components such as Formin1","No mechanism for how the PCR spatially organizes actomyosin during invasion"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Pcr4-Pcr5 heterodimer (preconoidal ring structural complex)"],"partners":["PCR5","FORMIN1 (RECRUITED TO THE PCR HUB)"],"other_free_text":["Pcr4 contains a B-box zinc-finger domain [#0].","Pcr4 is essential for preconoidal ring formation in Toxoplasma gondii [#0].","The Pcr4-dependent PCR serves as an assembly hub linking conoid architecture to actomyosin-driven gliding motility [#1].","Pcr4 and Pcr5 are conserved PCR components across Apicomplexa [#2]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"36109645","id":"PMC_36109645","title":"Conoid extrusion regulates glideosome assembly to control motility and invasion in Apicomplexa.","date":"2022","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/36109645","citation_count":37,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2848,"output_tokens":782,"usd":0.010137,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5567,"output_tokens":2098,"usd":0.040142,"stage2_stop_reason":"end_turn"},"total_usd":0.050279,"stage1_batch_id":"msgbatch_018xTxyBPcQFK9jdgubtxgsj","stage2_batch_id":"msgbatch_01UiG5BTaJP7BvKKL6RLeyv2","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"Pcr4 and Pcr5, which contain B-box zinc-finger domains, assemble as a heterodimer and are essential for the formation of the preconoidal rings (PCRs) in Toxoplasma gondii.\",\n      \"method\": \"Ultrastructure expansion microscopy, genetic loss-of-function (essentiality screens), protein interaction/assembly analysis\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct imaging with ultrastructure expansion microscopy plus loss-of-function demonstrating essentiality, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"36109645\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The preconoidal rings (PCRs), whose formation requires Pcr4, serve as a hub for glideosome components including Formin1, linking the PCR structure to actomyosin-based gliding motility.\",\n      \"method\": \"Ultrastructure expansion microscopy, co-localization of glideosome components at the PCR hub\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ultrastructure expansion microscopy with functional co-localization data, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"36109645\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Pcr4 and Pcr5 are conserved components of the preconoidal rings across Apicomplexa, indicating the heterodimeric B-box zinc-finger complex is a conserved structural element of the PCR in this phylum.\",\n      \"method\": \"Comparative genomics/sequence analysis combined with experimental localization and functional studies in Toxoplasma gondii\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — conservation inferred from sequence analysis plus experimental validation in Toxoplasma; cross-organism conservation not directly tested by reconstitution in other species\",\n      \"pmids\": [\"36109645\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"Pcr4 contains a B-box zinc-finger domain, forms an essential heterodimer with Pcr5 to build the preconoidal rings (PCRs), and these rings serve as an assembly hub for glideosome components (including Formin1), thereby linking conoid architecture to actomyosin-driven motility and invasion in Toxoplasma gondii.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Pcr4 is a B-box zinc-finger protein that functions as an essential structural component of the preconoidal rings (PCRs) at the apical conoid of Toxoplasma gondii [#0]. It assembles into a heterodimer with Pcr5, and this complex is required for PCR formation [#0]. The PCRs built through Pcr4 serve as an assembly hub for glideosome components, including Formin1, thereby physically linking conoid architecture to the actomyosin machinery that drives gliding motility [#1]. Pcr4 and its partner Pcr5 are conserved across Apicomplexa, indicating the heterodimeric B-box complex is a conserved structural element of the PCR in this phylum [#2]. Beyond its role in PCR assembly and glideosome recruitment [#0, #1], no further biochemical or structural mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Establishing what builds the preconoidal rings and whether specific proteins are essential answered a fundamental question about conoid architecture, identifying Pcr4 as a B-box zinc-finger protein that heterodimerizes with Pcr5 to form the PCRs.\",\n      \"evidence\": \"Ultrastructure expansion microscopy with genetic loss-of-function/essentiality analysis and protein assembly studies in Toxoplasma gondii\",\n      \"pmids\": [\"36109645\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of the Pcr4-Pcr5 heterodimer or the ring assembly is resolved\",\n        \"The role of the B-box zinc-finger domain in mediating heterodimerization is not dissected\",\n        \"How the heterodimer nucleates or is recruited to the preconoidal site is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Determining how the conoid structure connects to motility showed that the Pcr4-dependent PCRs act as a hub recruiting glideosome components including Formin1, linking the apical structure to actomyosin-based gliding.\",\n      \"evidence\": \"Ultrastructure expansion microscopy with co-localization of glideosome components at the PCR hub in Toxoplasma gondii\",\n      \"pmids\": [\"36109645\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct physical interaction between Pcr4 and Formin1 is not demonstrated\",\n        \"The mechanistic contribution of the PCR to actin nucleation or motility output is not quantified\",\n        \"Whether loss of Pcr4 abolishes motility through loss of glideosome recruitment specifically is not isolated\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Assessing evolutionary breadth indicated that the Pcr4-Pcr5 heterodimeric B-box complex is a conserved structural element of the PCR across Apicomplexa.\",\n      \"evidence\": \"Comparative genomics/sequence analysis with experimental localization and functional validation in Toxoplasma gondii\",\n      \"pmids\": [\"36109645\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Conservation is inferred from sequence analysis and not directly tested by reconstitution or functional assay in other apicomplexan species\",\n        \"Whether orthologs perform identical PCR and glideosome-hub functions in other species is untested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical basis of Pcr4 function — how its B-box domain drives heterodimerization, the atomic structure of the PCR, and the direct molecular links to specific glideosome proteins — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural or biophysical characterization of the Pcr4-Pcr5 complex\",\n        \"No direct binding data between Pcr4 and glideosome components such as Formin1\",\n        \"No mechanism for how the PCR spatially organizes actomyosin during invasion\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008270\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071966\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"Pcr4-Pcr5 heterodimer (preconoidal ring structural complex)\"\n    ],\n    \"partners\": [\n      \"Pcr5\",\n      \"Formin1 (recruited to the PCR hub)\"\n    ],\n    \"other_free_text\": [\n      \"Pcr4 contains a B-box zinc-finger domain [#0].\",\n      \"Pcr4 is essential for preconoidal ring formation in Toxoplasma gondii [#0].\",\n      \"The Pcr4-dependent PCR serves as an assembly hub linking conoid architecture to actomyosin-driven gliding motility [#1].\",\n      \"Pcr4 and Pcr5 are conserved PCR components across Apicomplexa [#2].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_201220","name":"PCR4","product":"preconoidal ring protein PCR4","uniprot_acc":"A0A125YV87","chromosome":"TGME49_chrVIIa","start_pos":3960592},{"strain":"GT1","gene_id":"TGGT1_201220","name":null,"product":"zinc finger protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIIa","start_pos":3861879},{"strain":"RH88","gene_id":"TGRH88_037430","name":null,"product":"zinc finger protein","uniprot_acc":null,"chromosome":"CM023088","start_pos":4055780},{"strain":"VEG","gene_id":"TGVEG_201220","name":null,"product":"zinc finger protein","uniprot_acc":"B9PUV4","chromosome":"TGVEG_chrVIIa","start_pos":4050535}]}