{"gene":"TG_242320","gene_symbol":"PCR5","run_date":"2026-09-08T12:58:25","timeline":{"discoveries":[{"year":2022,"finding":"Preconoidal rings (PCRs) serve as a hub for glideosome components including Formin1, as established by ultrastructure expansion microscopy.","method":"Ultrastructure expansion microscopy (U-ExM)","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence, single lab, ultrastructure expansion microscopy with functional follow-up","pmids":["36109645"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Pcr5 contains a B-box zinc-finger domain, assembles as a heterodimer with Pcr4, and is essential for the formation of the preconoidal ring structure.","method":"Ultrastructure expansion microscopy, genetic perturbation (essentiality screen), protein interaction/complex assembly analysis","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct structural and functional characterization in a single lab with multiple orthogonal approaches (localization, domain identification, loss-of-function, complex assembly)","pmids":["36109645"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Pcr5 (and Pcr4) are conserved components of preconoidal rings across Apicomplexa, placing them in an apical structural hub that gates parasite motility and invasion through control of conoid extrusion and F-actin flux.","method":"Comparative genomics combined with ultrastructure expansion microscopy and functional (motility/invasion) assays","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pathway placement supported by loss-of-function phenotypes (motility, invasion) and localization, single lab","pmids":["36109645"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"PCR5 (Pcr5) is a B-box zinc-finger domain-containing protein that forms an essential heterodimer with Pcr4 at the preconoidal rings of Toxoplasma gondii, where it is required for preconoidal ring structure formation and acts as part of an apical hub that recruits glideosome components (including Formin1) to regulate conoid extrusion, F-actin flux, and thereby parasite motility and invasion."},"narrative":{"mechanistic_narrative":"PCR5 (Pcr5) is a structural component of the preconoidal rings (PCRs) at the apical tip of Toxoplasma gondii, where it participates in an apical hub that gates parasite motility and invasion [PMID:36109645]. It contains a B-box zinc-finger domain and assembles as a heterodimer with Pcr4, an interaction essential for formation of the preconoidal ring structure itself [PMID:36109645]. The PCRs serve as a recruitment hub for glideosome components including Formin1, thereby coupling apical ring architecture to conoid extrusion and F-actin flux that drive motility and host-cell invasion [PMID:36109645]. Beyond this PCR structural and glideosome-recruitment role established in T. gondii, no further biochemical or mechanistic detail for PCR5 has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"Establishing where glideosome activity is organized at the parasite apex, the preconoidal rings were shown to serve as a hub for glideosome components, linking an apical ultrastructure to the motility machinery.","evidence":"Ultrastructure expansion microscopy localizing Formin1 and other glideosome components to the PCRs in Toxoplasma gondii","pmids":["36109645"],"confidence":"Medium","gaps":["Does not define the direct binding interactions between PCR proteins and recruited glideosome factors","Molecular mechanism by which the PCR hub controls conoid extrusion is not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"To define what builds the preconoidal ring, Pcr5 was identified as a B-box zinc-finger protein that heterodimerizes with Pcr4 and is essential for ring formation, establishing it as a required structural subunit rather than a peripheral component.","evidence":"U-ExM localization, essentiality/genetic perturbation, and protein interaction/complex assembly analysis in Toxoplasma gondii","pmids":["36109645"],"confidence":"Medium","gaps":["No structural model of the Pcr4-Pcr5 heterodimer or its arrangement within the ring","Role of the B-box zinc-finger domain in dimerization or ring assembly not dissected","Whether Pcr5 directly contacts glideosome components is not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"To place PCR5 in a biological pathway, the Pcr4/Pcr5 module was shown to be conserved across Apicomplexa and to gate motility and invasion through control of conoid extrusion and F-actin flux, defining the functional output of the apical hub.","evidence":"Comparative genomics with U-ExM and motility/invasion functional assays in Toxoplasma gondii","pmids":["36109645"],"confidence":"Medium","gaps":["Mechanistic coupling between ring integrity and F-actin flux is not defined","Contribution of PCR5 in other apicomplexan species not experimentally tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How the Pcr4/Pcr5 heterodimer mechanically transmits signals or scaffolds glideosome components to control conoid extrusion and actin dynamics remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct biochemical map of PCR5 partner contacts beyond the Pcr4 heterodimer","No high-resolution structure of the assembled preconoidal ring"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Pcr4-Pcr5 heterodimer at the preconoidal rings"],"partners":["PCR4","FORMIN1 (GLIDEOSOME COMPONENT RECRUITED TO PRECONOIDAL RINGS)"],"other_free_text":["Contains a B-box zinc-finger domain [#1]","Essential for preconoidal ring structure formation [#1]","Part of an apical hub controlling conoid extrusion, F-actin flux, motility, and invasion [#2]","Conserved 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":745,"usd":0.00986,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5530,"output_tokens":1937,"usd":0.038038,"stage2_stop_reason":"end_turn"},"total_usd":0.047898,"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\": \"Preconoidal rings (PCRs) serve as a hub for glideosome components including Formin1, as established by ultrastructure expansion microscopy.\",\n      \"method\": \"Ultrastructure expansion microscopy (U-ExM)\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence, single lab, ultrastructure expansion microscopy with functional follow-up\",\n      \"pmids\": [\"36109645\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Pcr5 contains a B-box zinc-finger domain, assembles as a heterodimer with Pcr4, and is essential for the formation of the preconoidal ring structure.\",\n      \"method\": \"Ultrastructure expansion microscopy, genetic perturbation (essentiality screen), protein interaction/complex assembly analysis\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct structural and functional characterization in a single lab with multiple orthogonal approaches (localization, domain identification, loss-of-function, complex assembly)\",\n      \"pmids\": [\"36109645\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Pcr5 (and Pcr4) are conserved components of preconoidal rings across Apicomplexa, placing them in an apical structural hub that gates parasite motility and invasion through control of conoid extrusion and F-actin flux.\",\n      \"method\": \"Comparative genomics combined with ultrastructure expansion microscopy and functional (motility/invasion) assays\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pathway placement supported by loss-of-function phenotypes (motility, invasion) and localization, single lab\",\n      \"pmids\": [\"36109645\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PCR5 (Pcr5) is a B-box zinc-finger domain-containing protein that forms an essential heterodimer with Pcr4 at the preconoidal rings of Toxoplasma gondii, where it is required for preconoidal ring structure formation and acts as part of an apical hub that recruits glideosome components (including Formin1) to regulate conoid extrusion, F-actin flux, and thereby parasite motility and invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PCR5 (Pcr5) is a structural component of the preconoidal rings (PCRs) at the apical tip of Toxoplasma gondii, where it participates in an apical hub that gates parasite motility and invasion [#2]. It contains a B-box zinc-finger domain and assembles as a heterodimer with Pcr4, an interaction essential for formation of the preconoidal ring structure itself [#1]. The PCRs serve as a recruitment hub for glideosome components including Formin1, thereby coupling apical ring architecture to conoid extrusion and F-actin flux that drive motility and host-cell invasion [#0, #2]. Beyond this PCR structural and glideosome-recruitment role established in T. gondii, no further biochemical or mechanistic detail for PCR5 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Establishing where glideosome activity is organized at the parasite apex, the preconoidal rings were shown to serve as a hub for glideosome components, linking an apical ultrastructure to the motility machinery.\",\n      \"evidence\": \"Ultrastructure expansion microscopy localizing Formin1 and other glideosome components to the PCRs in Toxoplasma gondii\",\n      \"pmids\": [\"36109645\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Does not define the direct binding interactions between PCR proteins and recruited glideosome factors\",\n        \"Molecular mechanism by which the PCR hub controls conoid extrusion is not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To define what builds the preconoidal ring, Pcr5 was identified as a B-box zinc-finger protein that heterodimerizes with Pcr4 and is essential for ring formation, establishing it as a required structural subunit rather than a peripheral component.\",\n      \"evidence\": \"U-ExM localization, essentiality/genetic perturbation, and protein interaction/complex assembly analysis in Toxoplasma gondii\",\n      \"pmids\": [\"36109645\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No structural model of the Pcr4-Pcr5 heterodimer or its arrangement within the ring\",\n        \"Role of the B-box zinc-finger domain in dimerization or ring assembly not dissected\",\n        \"Whether Pcr5 directly contacts glideosome components is not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To place PCR5 in a biological pathway, the Pcr4/Pcr5 module was shown to be conserved across Apicomplexa and to gate motility and invasion through control of conoid extrusion and F-actin flux, defining the functional output of the apical hub.\",\n      \"evidence\": \"Comparative genomics with U-ExM and motility/invasion functional assays in Toxoplasma gondii\",\n      \"pmids\": [\"36109645\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Mechanistic coupling between ring integrity and F-actin flux is not defined\",\n        \"Contribution of PCR5 in other apicomplexan species not experimentally tested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the Pcr4/Pcr5 heterodimer mechanically transmits signals or scaffolds glideosome components to control conoid extrusion and actin dynamics remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No direct biochemical map of PCR5 partner contacts beyond the Pcr4 heterodimer\",\n        \"No high-resolution structure of the assembled preconoidal ring\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020015\", \"supporting_discovery_ids\": [0, 1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0052126\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"Pcr4-Pcr5 heterodimer at the preconoidal rings\"\n    ],\n    \"partners\": [\n      \"Pcr4\",\n      \"Formin1 (glideosome component recruited to preconoidal rings)\"\n    ],\n    \"other_free_text\": [\n      \"Contains a B-box zinc-finger domain [#1]\",\n      \"Essential for preconoidal ring structure formation [#1]\",\n      \"Part of an apical hub controlling conoid extrusion, F-actin flux, motility, and invasion [#2]\",\n      \"Conserved across Apicomplexa [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_242320","name":"PCR5","product":"preconoidal ring protein PCR5","uniprot_acc":"A0A125YZK2","chromosome":"TGME49_chrVI","start_pos":1954529},{"strain":"GT1","gene_id":"TGGT1_242320","name":null,"product":"B-box zinc finger domain-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrVI","start_pos":1865178},{"strain":"RH88","gene_id":"TGRH88_029750","name":null,"product":"B-box zinc finger domain-containing protein","uniprot_acc":null,"chromosome":"CM023087","start_pos":1758373},{"strain":"VEG","gene_id":"TGVEG_242320","name":null,"product":"B-box zinc finger domain-containing protein","uniprot_acc":"B6KFN1","chromosome":"TGVEG_chrVI","start_pos":1957723}]}