{"gene":"TG_309810","gene_symbol":"RPP2","run_date":"2026-09-08T15:15:13","timeline":{"discoveries":[{"year":2014,"finding":"TgP2 (RPP2) localizes to the surface of free tachyzoites, as confirmed by localization of epitope-tagged P2 transfected in T. gondii; unlike its P. falciparum ortholog, TgP2 does not localize to the host cell membrane in infected human foreskin fibroblast cells, and exhibits only weak SDS-resistant dimerization rather than the stable oligomers formed by PfP2.","method":"Epitope-tagged transfection and live/immunofluorescence localization; circular dichroism spectroscopy; SDS-PAGE oligomerization assay","journal":"Parasitology international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epitope-tag localization with fractionation, CD spectroscopy, and oligomerization assay in a single study; single lab but multiple orthogonal methods","pmids":["25280460"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"finding":"Antibodies raised against TgP2 (RPP2) blocked T. gondii tachyzoite invasion of host cells, demonstrating a functional role for surface-localized P2 in host cell invasion.","method":"Invasion inhibition assay using anti-P2 antibodies","journal":"Parasitology international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional invasion inhibition assay with specific antibodies, single lab, corroborated by parallel results in P. falciparum","pmids":["25280460"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"finding":"The C-terminal domain (~50 aa) of TgP2 (RPP2) is intrinsically disordered, lacking stable secondary structure, but contains short segments with preferred secondary structural propensities; gel filtration indicated monomer-multimer equilibrium at millimolar concentrations.","method":"NMR (1H-15N HSQC), circular dichroism spectroscopy, gel filtration chromatography of recombinant C-terminal domain","journal":"Protein and peptide letters","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — NMR and CD structural characterization with multiple orthogonal biophysical methods; single lab, comparative study across three species","pmids":["25412900"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"Recombinant TgRPP2 binds to murine macrophage Ana-1 cells and modulates their proliferation, apoptosis, phagocytosis, nitric oxide production, and cytokine secretion in vitro, indicating an extracellular immunomodulatory function for the surface-localized ribosomal protein.","method":"Recombinant protein binding assay to Ana-1 macrophages; cell proliferation, apoptosis, phagocytosis, NO production, and cytokine assays in vitro","journal":"Vaccines","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, in vitro functional assays with recombinant protein on a heterologous (murine) cell system; no genetic KO/KI in parasite","pmids":["33917244"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgRPP2 is a conserved acidic ribosomal stalk protein that, beyond its canonical ribosomal role, localizes to the surface of free tachyzoites (confirmed by epitope-tag imaging), where surface-directed antibodies block host cell invasion; its isolated C-terminal domain is intrinsically disordered with transient secondary structure propensities and undergoes monomer-multimer equilibrium, and recombinant TgRPP2 can bind to and modulate macrophage functions extracellularly."},"narrative":{"mechanistic_narrative":"TgRPP2 (TgP2) is an acidic ribosomal stalk protein of Toxoplasma gondii that additionally moonlights at the tachyzoite surface, where it participates in host cell invasion [PMID:25280460]. Epitope-tagged TgP2 localizes to the surface of free tachyzoites, and — unlike its Plasmodium falciparum ortholog — it does not relocate to the host cell membrane of infected fibroblasts and forms only weak SDS-resistant dimers rather than stable oligomers [PMID:25280460]. Antibodies directed against surface TgP2 block tachyzoite invasion, establishing a functional role for the surface-exposed pool in host cell entry [PMID:25280460]. Structurally, its ~50-residue C-terminal domain is intrinsically disordered, retaining only short segments with transient secondary-structure propensity, and it exists in a concentration-dependent monomer–multimer equilibrium [PMID:25412900]. Beyond invasion, recombinant TgRPP2 binds murine macrophages and modulates their proliferation, apoptosis, phagocytosis, nitric oxide production, and cytokine secretion, pointing to an extracellular immunomodulatory activity [PMID:33917244].","teleology":[{"year":2014,"claim":"It was unknown whether the Toxoplasma ribosomal stalk protein P2 had any extra-ribosomal localization; epitope-tag imaging showed it reaches the free tachyzoite surface, distinguishing it from the host-membrane-targeting Plasmodium ortholog and revealing a moonlighting distribution.","evidence":"Epitope-tagged transfection with live/immunofluorescence localization, plus CD spectroscopy and SDS-PAGE oligomerization assay in T. gondii","pmids":["25280460"],"confidence":"Medium","gaps":["mechanism of surface trafficking of a ribosomal protein not defined","no genetic knockout to test endogenous requirement","relationship between the ribosomal and surface pools unquantified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"claim":"Whether surface P2 contributes functionally to infection was open; antibody blockade of invasion demonstrated that the surface-localized protein is required for efficient tachyzoite entry into host cells.","evidence":"Invasion inhibition assay using anti-P2 antibodies in T. gondii","pmids":["25280460"],"confidence":"Medium","gaps":["host receptor or binding partner mediating invasion not identified","antibody blockade does not distinguish direct adhesion from downstream steps"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"claim":"The structural basis of the functional C-terminus was unknown; NMR and CD showed it is intrinsically disordered with only transient secondary-structure propensity and a monomer-multimer equilibrium, framing its interactions as those of a flexible domain.","evidence":"NMR (1H-15N HSQC), CD spectroscopy, and gel filtration of the recombinant C-terminal domain","pmids":["25412900"],"confidence":"Medium","gaps":["no structure of the full-length protein or ribosome-bound form","functional consequence of the disorder for invasion not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"Whether surface/secreted TgRPP2 acts on host immune cells was unaddressed; recombinant protein bound macrophages and altered their proliferation, apoptosis, phagocytosis, NO output, and cytokines, indicating an extracellular immunomodulatory role.","evidence":"Recombinant TgRPP2 binding and functional assays on murine Ana-1 macrophages in vitro","pmids":["33917244"],"confidence":"Low","gaps":["in vitro recombinant protein on a heterologous murine cell line; no parasite genetic manipulation","macrophage receptor for TgRPP2 not identified","relevance to in vivo infection unestablished"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The molecular partners that link surface TgRPP2 to invasion and to macrophage engagement, and the trafficking route that delivers a ribosomal protein to the tachyzoite surface, remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["no host receptor identified for invasion or immunomodulation","no genetic loss-of-function evidence for the endogenous protein","surface-targeting mechanism uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Surface-localized on free tachyzoites; anti-TgP2 antibodies block host cell invasion [#0, #1]","C-terminal ~50-aa domain intrinsically disordered with transient secondary-structure propensity and monomer-multimer equilibrium [#2]","Recombinant TgRPP2 binds and immunomodulates murine macrophages (proliferation, apoptosis, phagocytosis, NO, cytokines) in vitro [#3]","Forms only weak SDS-resistant dimers, unlike the stable oligomers of the P. falciparum ortholog [#0]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"25280460","id":"PMC_25280460","title":"Ribosomal protein P2 localizes to the parasite zoite-surface and is a target for invasion inhibitory antibodies in Toxoplasma gondii and Plasmodium falciparum.","date":"2014","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/25280460","citation_count":11,"is_preprint":false},{"pmid":"33917244","id":"PMC_33917244","title":"Recombinant Toxoplasma gondii Ribosomal Protein P2 Modulates the Functions of Murine Macrophages In Vitro and Provides Immunity against Acute Toxoplasmosis In Vivo.","date":"2021","source":"Vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/33917244","citation_count":9,"is_preprint":false},{"pmid":"25412900","id":"PMC_25412900","title":"The C-terminal domain of eukaryotic acidic ribosomal P2 proteins is intrinsically disordered with conserved structural propensities.","date":"2014","source":"Protein and peptide letters","url":"https://pubmed.ncbi.nlm.nih.gov/25412900","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3993,"output_tokens":1169,"usd":0.014757,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6075,"output_tokens":2312,"usd":0.044088,"stage2_stop_reason":"end_turn"},"total_usd":0.058845,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"TgP2 (RPP2) localizes to the surface of free tachyzoites, as confirmed by localization of epitope-tagged P2 transfected in T. gondii; unlike its P. falciparum ortholog, TgP2 does not localize to the host cell membrane in infected human foreskin fibroblast cells, and exhibits only weak SDS-resistant dimerization rather than the stable oligomers formed by PfP2.\",\n      \"method\": \"Epitope-tagged transfection and live/immunofluorescence localization; circular dichroism spectroscopy; SDS-PAGE oligomerization assay\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epitope-tag localization with fractionation, CD spectroscopy, and oligomerization assay in a single study; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"25280460\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Antibodies raised against TgP2 (RPP2) blocked T. gondii tachyzoite invasion of host cells, demonstrating a functional role for surface-localized P2 in host cell invasion.\",\n      \"method\": \"Invasion inhibition assay using anti-P2 antibodies\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional invasion inhibition assay with specific antibodies, single lab, corroborated by parallel results in P. falciparum\",\n      \"pmids\": [\"25280460\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The C-terminal domain (~50 aa) of TgP2 (RPP2) is intrinsically disordered, lacking stable secondary structure, but contains short segments with preferred secondary structural propensities; gel filtration indicated monomer-multimer equilibrium at millimolar concentrations.\",\n      \"method\": \"NMR (1H-15N HSQC), circular dichroism spectroscopy, gel filtration chromatography of recombinant C-terminal domain\",\n      \"journal\": \"Protein and peptide letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR and CD structural characterization with multiple orthogonal biophysical methods; single lab, comparative study across three species\",\n      \"pmids\": [\"25412900\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Recombinant TgRPP2 binds to murine macrophage Ana-1 cells and modulates their proliferation, apoptosis, phagocytosis, nitric oxide production, and cytokine secretion in vitro, indicating an extracellular immunomodulatory function for the surface-localized ribosomal protein.\",\n      \"method\": \"Recombinant protein binding assay to Ana-1 macrophages; cell proliferation, apoptosis, phagocytosis, NO production, and cytokine assays in vitro\",\n      \"journal\": \"Vaccines\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, in vitro functional assays with recombinant protein on a heterologous (murine) cell system; no genetic KO/KI in parasite\",\n      \"pmids\": [\"33917244\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgRPP2 is a conserved acidic ribosomal stalk protein that, beyond its canonical ribosomal role, localizes to the surface of free tachyzoites (confirmed by epitope-tag imaging), where surface-directed antibodies block host cell invasion; its isolated C-terminal domain is intrinsically disordered with transient secondary structure propensities and undergoes monomer-multimer equilibrium, and recombinant TgRPP2 can bind to and modulate macrophage functions extracellularly.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgRPP2 (TgP2) is an acidic ribosomal stalk protein of Toxoplasma gondii that additionally moonlights at the tachyzoite surface, where it participates in host cell invasion [#0, #1]. Epitope-tagged TgP2 localizes to the surface of free tachyzoites, and — unlike its Plasmodium falciparum ortholog — it does not relocate to the host cell membrane of infected fibroblasts and forms only weak SDS-resistant dimers rather than stable oligomers [#0]. Antibodies directed against surface TgP2 block tachyzoite invasion, establishing a functional role for the surface-exposed pool in host cell entry [#1]. Structurally, its ~50-residue C-terminal domain is intrinsically disordered, retaining only short segments with transient secondary-structure propensity, and it exists in a concentration-dependent monomer–multimer equilibrium [#2]. Beyond invasion, recombinant TgRPP2 binds murine macrophages and modulates their proliferation, apoptosis, phagocytosis, nitric oxide production, and cytokine secretion, pointing to an extracellular immunomodulatory activity [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"It was unknown whether the Toxoplasma ribosomal stalk protein P2 had any extra-ribosomal localization; epitope-tag imaging showed it reaches the free tachyzoite surface, distinguishing it from the host-membrane-targeting Plasmodium ortholog and revealing a moonlighting distribution.\",\n      \"evidence\": \"Epitope-tagged transfection with live/immunofluorescence localization, plus CD spectroscopy and SDS-PAGE oligomerization assay in T. gondii\",\n      \"pmids\": [\"25280460\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"mechanism of surface trafficking of a ribosomal protein not defined\",\n        \"no genetic knockout to test endogenous requirement\",\n        \"relationship between the ribosomal and surface pools unquantified\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether surface P2 contributes functionally to infection was open; antibody blockade of invasion demonstrated that the surface-localized protein is required for efficient tachyzoite entry into host cells.\",\n      \"evidence\": \"Invasion inhibition assay using anti-P2 antibodies in T. gondii\",\n      \"pmids\": [\"25280460\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"host receptor or binding partner mediating invasion not identified\",\n        \"antibody blockade does not distinguish direct adhesion from downstream steps\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"The structural basis of the functional C-terminus was unknown; NMR and CD showed it is intrinsically disordered with only transient secondary-structure propensity and a monomer-multimer equilibrium, framing its interactions as those of a flexible domain.\",\n      \"evidence\": \"NMR (1H-15N HSQC), CD spectroscopy, and gel filtration of the recombinant C-terminal domain\",\n      \"pmids\": [\"25412900\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no structure of the full-length protein or ribosome-bound form\",\n        \"functional consequence of the disorder for invasion not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether surface/secreted TgRPP2 acts on host immune cells was unaddressed; recombinant protein bound macrophages and altered their proliferation, apoptosis, phagocytosis, NO output, and cytokines, indicating an extracellular immunomodulatory role.\",\n      \"evidence\": \"Recombinant TgRPP2 binding and functional assays on murine Ana-1 macrophages in vitro\",\n      \"pmids\": [\"33917244\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"in vitro recombinant protein on a heterologous murine cell line; no parasite genetic manipulation\",\n        \"macrophage receptor for TgRPP2 not identified\",\n        \"relevance to in vivo infection unestablished\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular partners that link surface TgRPP2 to invasion and to macrophage engagement, and the trafficking route that delivers a ribosomal protein to the tachyzoite surface, remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no host receptor identified for invasion or immunomodulation\",\n        \"no genetic loss-of-function evidence for the endogenous protein\",\n        \"surface-targeting mechanism uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003735\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Surface-localized on free tachyzoites; anti-TgP2 antibodies block host cell invasion [#0, #1]\",\n      \"C-terminal ~50-aa domain intrinsically disordered with transient secondary-structure propensity and monomer-multimer equilibrium [#2]\",\n      \"Recombinant TgRPP2 binds and immunomodulates murine macrophages (proliferation, apoptosis, phagocytosis, NO, cytokines) in vitro [#3]\",\n      \"Forms only weak SDS-resistant dimers, unlike the stable oligomers of the P. falciparum ortholog [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_309810","name":"RPP2","product":"ribosomal protein RPP2","uniprot_acc":"A0A125YFT4","chromosome":"TGME49_chrXI","start_pos":828439},{"strain":"GT1","gene_id":"TGGT1_309810","name":null,"product":"ribosomal protein RPP2","uniprot_acc":null,"chromosome":"TGGT1_chrXI","start_pos":791021},{"strain":"RH88","gene_id":"TGRH88_049300","name":null,"product":"ribosomal protein RPP2","uniprot_acc":null,"chromosome":"CM023092","start_pos":876758},{"strain":"VEG","gene_id":"TGVEG_309810","name":null,"product":"ribosomal protein RPP2","uniprot_acc":"B9PJK1","chromosome":"TGVEG_chrXI","start_pos":837638}]}