{"gene":"PF3D7_1426000","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2014,"finding":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution was determined; RPL21 (PF3D7_1426000) is a constituent protein of the 60S large subunit of this ribosome complex, as visualized in the structure bound to emetine.","method":"Cryo-EM structure determination at 3.2 Å resolution","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure establishes complex membership, but no functional experiment specifically probes RPL21 itself; single study","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Cryo-EM reconstructions of P. falciparum blood-stage schizont ribosomes at sub-nanometer resolution confirmed RPL21 (PF3D7_1426000) as a structural component of the 60S subunit of the parasite 80S ribosome; atomic models were built by flexible fitting into the density maps.","method":"Cryo-EM with multiple reconstructions and atomic model building by flexible fitting","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — sub-nanometer cryo-EM with atomic models, but no functional experiment specifically isolates RPL21; single lab","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å with mefloquine bound confirmed RPL21 (PF3D7_1426000) as a structural component of the 60S large subunit; the ribosome complex including RPL21 is the functional target through which mefloquine inhibits protein synthesis.","method":"Cryo-EM at 3.2 Å resolution; mutagenesis of binding-site residues confirming mechanism","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM plus mutagenesis validation, but mutagenesis targets other ribosomal residues, not RPL21 specifically; single study","pmids":["28288098"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In situ cryo-electron tomography of native P. falciparum-infected erythrocytes at high resolution placed RPL21 (PF3D7_1426000) within the actively translating 80S ribosome complex; drug perturbation with a Plasmodium-specific translation inhibitor altered elongation factor-bound ribosomal states and apparently upregulated ribosome biogenesis, providing a cellular-context view of the ribosome complex of which RPL21 is a member.","method":"In situ cryo-electron tomography; eight high-resolution structures from native infected erythrocytes; drug perturbation experiment","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in situ cryo-ET with multiple structures in native context, but no experiment specifically addresses RPL21 function; single study","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"RPL21 (PF3D7_1426000) is established as a structural component of the 60S large subunit of the P. falciparum cytoplasmic 80S ribosome, as visualized in multiple cryo-EM and in situ cryo-ET structures; no experiment has specifically probed the function, interactions, or modifications of RPL21 itself beyond its membership in the ribosome complex."},"narrative":{"mechanistic_narrative":"RPL21 (PF3D7_1426000) is a structural constituent protein of the 60S large subunit of the Plasmodium falciparum cytoplasmic 80S ribosome, as visualized in successive high-resolution cryo-EM structures of the parasite ribosome [PMID:24913268, PMID:26432834]. It is present within the assembled 60S subunit that forms the functional target of translation-inhibiting antimalarials, including emetine and mefloquine, which act on the ribosome complex to block protein synthesis [PMID:24913268, PMID:28288098], and it is positioned within actively translating 80S ribosomes observed in the native cellular context of infected erythrocytes by in situ cryo-electron tomography [PMID:40825879]. Beyond this membership in the ribosome complex, no experiment in the available corpus has specifically probed the function, interactions, or modifications of RPL21 itself; its role is defined entirely by its participation in the 60S subunit.","teleology":[{"year":2014,"claim":"Establishing whether PF3D7_1426000 is a component of the parasite ribosome answered where this protein resides functionally, placing it within the 60S large subunit of the 80S ribosome.","evidence":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å bound to emetine","pmids":["24913268"],"confidence":"Medium","gaps":["No functional experiment isolates RPL21 or tests its specific contribution to translation","No RPL21-specific interactions or post-translational modifications characterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Independent cryo-EM reconstructions of blood-stage schizont ribosomes confirmed RPL21 as a reproducible structural member of the 60S subunit across atomic models built by flexible fitting.","evidence":"Sub-nanometer cryo-EM reconstructions with atomic model building in P. falciparum schizonts","pmids":["26432834"],"confidence":"Medium","gaps":["Structural membership only; no assay of RPL21 function or assembly role","Single lab confirmation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Structural determination of the ribosome with mefloquine bound clarified that the 60S-containing complex of which RPL21 is a part is the target through which the drug inhibits protein synthesis.","evidence":"Cryo-EM at 3.2 Å with mefloquine bound and mutagenesis of binding-site residues in P. falciparum","pmids":["28288098"],"confidence":"Medium","gaps":["Mutagenesis targeted other ribosomal residues, not RPL21","RPL21's specific role in the drug interaction not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"In situ cryo-electron tomography extended the picture from purified complexes to the native cellular context, placing RPL21 within actively translating ribosomes and revealing drug-induced shifts in ribosomal states and biogenesis.","evidence":"In situ cryo-ET of native P. falciparum-infected erythrocytes yielding eight high-resolution structures plus drug perturbation","pmids":["40825879"],"confidence":"Medium","gaps":["No experiment specifically addresses RPL21 function within translating ribosomes","Cellular-context view does not resolve RPL21-specific dynamics or interactions"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether RPL21 has any function, interaction, or regulatory feature beyond passive membership in the 60S subunit remains uncharacterized.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No RPL21-specific loss-of-function, knockdown, or biochemical assay exists in the corpus","No RPL21 post-translational modifications or extra-ribosomal roles characterized","No RPL21-specific binding partners identified beyond the ribosome complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["60S large ribosomal subunit of the P. falciparum cytoplasmic 80S ribosome"],"partners":[],"other_free_text":["RPL21 (PF3D7_1426000) is characterized in the corpus solely as a structural constituent of the 60S subunit; no function, interaction, or modification specific to RPL21 has been experimentally probed.","The ribosome complex containing RPL21 is the functional target of the antimalarials emetine and mefloquine, though the drug-binding residues characterized are on other ribosomal components, not RPL21."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24913268","id":"PMC_24913268","title":"Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine.","date":"2014","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/24913268","citation_count":276,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28288098","id":"PMC_28288098","title":"Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis.","date":"2017","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28288098","citation_count":138,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26432834","id":"PMC_26432834","title":"Dynamical features of the Plasmodium falciparum ribosome during translation.","date":"2015","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/26432834","citation_count":46,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40825879","id":"PMC_40825879","title":"Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug.","date":"2025","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/40825879","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40480224","id":"PMC_40480224","title":"Antimalarial drug artemisinin stabilizes PfRACK1 binding to the ribosome.","date":"2025","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/40480224","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4836,"output_tokens":1147,"usd":0.015856,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5960,"output_tokens":2027,"usd":0.040238,"stage2_stop_reason":"end_turn"},"total_usd":0.056094,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution was determined; RPL21 (PF3D7_1426000) is a constituent protein of the 60S large subunit of this ribosome complex, as visualized in the structure bound to emetine.\",\n      \"method\": \"Cryo-EM structure determination at 3.2 Å resolution\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM structure establishes complex membership, but no functional experiment specifically probes RPL21 itself; single study\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Cryo-EM reconstructions of P. falciparum blood-stage schizont ribosomes at sub-nanometer resolution confirmed RPL21 (PF3D7_1426000) as a structural component of the 60S subunit of the parasite 80S ribosome; atomic models were built by flexible fitting into the density maps.\",\n      \"method\": \"Cryo-EM with multiple reconstructions and atomic model building by flexible fitting\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — sub-nanometer cryo-EM with atomic models, but no functional experiment specifically isolates RPL21; single lab\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å with mefloquine bound confirmed RPL21 (PF3D7_1426000) as a structural component of the 60S large subunit; the ribosome complex including RPL21 is the functional target through which mefloquine inhibits protein synthesis.\",\n      \"method\": \"Cryo-EM at 3.2 Å resolution; mutagenesis of binding-site residues confirming mechanism\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM plus mutagenesis validation, but mutagenesis targets other ribosomal residues, not RPL21 specifically; single study\",\n      \"pmids\": [\"28288098\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In situ cryo-electron tomography of native P. falciparum-infected erythrocytes at high resolution placed RPL21 (PF3D7_1426000) within the actively translating 80S ribosome complex; drug perturbation with a Plasmodium-specific translation inhibitor altered elongation factor-bound ribosomal states and apparently upregulated ribosome biogenesis, providing a cellular-context view of the ribosome complex of which RPL21 is a member.\",\n      \"method\": \"In situ cryo-electron tomography; eight high-resolution structures from native infected erythrocytes; drug perturbation experiment\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in situ cryo-ET with multiple structures in native context, but no experiment specifically addresses RPL21 function; single study\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"RPL21 (PF3D7_1426000) is established as a structural component of the 60S large subunit of the P. falciparum cytoplasmic 80S ribosome, as visualized in multiple cryo-EM and in situ cryo-ET structures; no experiment has specifically probed the function, interactions, or modifications of RPL21 itself beyond its membership in the ribosome complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPL21 (PF3D7_1426000) is a structural constituent protein of the 60S large subunit of the Plasmodium falciparum cytoplasmic 80S ribosome, as visualized in successive high-resolution cryo-EM structures of the parasite ribosome [#0, #1]. It is present within the assembled 60S subunit that forms the functional target of translation-inhibiting antimalarials, including emetine and mefloquine, which act on the ribosome complex to block protein synthesis [#0, #2], and it is positioned within actively translating 80S ribosomes observed in the native cellular context of infected erythrocytes by in situ cryo-electron tomography [#3]. Beyond this membership in the ribosome complex, no experiment in the available corpus has specifically probed the function, interactions, or modifications of RPL21 itself; its role is defined entirely by its participation in the 60S subunit.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing whether PF3D7_1426000 is a component of the parasite ribosome answered where this protein resides functionally, placing it within the 60S large subunit of the 80S ribosome.\",\n      \"evidence\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å bound to emetine\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional experiment isolates RPL21 or tests its specific contribution to translation\",\n        \"No RPL21-specific interactions or post-translational modifications characterized\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Independent cryo-EM reconstructions of blood-stage schizont ribosomes confirmed RPL21 as a reproducible structural member of the 60S subunit across atomic models built by flexible fitting.\",\n      \"evidence\": \"Sub-nanometer cryo-EM reconstructions with atomic model building in P. falciparum schizonts\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural membership only; no assay of RPL21 function or assembly role\",\n        \"Single lab confirmation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Structural determination of the ribosome with mefloquine bound clarified that the 60S-containing complex of which RPL21 is a part is the target through which the drug inhibits protein synthesis.\",\n      \"evidence\": \"Cryo-EM at 3.2 Å with mefloquine bound and mutagenesis of binding-site residues in P. falciparum\",\n      \"pmids\": [\"28288098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mutagenesis targeted other ribosomal residues, not RPL21\",\n        \"RPL21's specific role in the drug interaction not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"In situ cryo-electron tomography extended the picture from purified complexes to the native cellular context, placing RPL21 within actively translating ribosomes and revealing drug-induced shifts in ribosomal states and biogenesis.\",\n      \"evidence\": \"In situ cryo-ET of native P. falciparum-infected erythrocytes yielding eight high-resolution structures plus drug perturbation\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No experiment specifically addresses RPL21 function within translating ribosomes\",\n        \"Cellular-context view does not resolve RPL21-specific dynamics or interactions\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether RPL21 has any function, interaction, or regulatory feature beyond passive membership in the 60S subunit remains uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No RPL21-specific loss-of-function, knockdown, or biochemical assay exists in the corpus\",\n        \"No RPL21 post-translational modifications or extra-ribosomal roles characterized\",\n        \"No RPL21-specific binding partners identified beyond the ribosome complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003735\", \"supporting_discovery_ids\": [0, 1, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0022625\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"complexes\": [\n      \"60S large ribosomal subunit of the P. falciparum cytoplasmic 80S ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"RPL21 (PF3D7_1426000) is characterized in the corpus solely as a structural constituent of the 60S subunit; no function, interaction, or modification specific to RPL21 has been experimentally probed.\",\n      \"The ribosome complex containing RPL21 is the functional target of the antimalarials emetine and mefloquine, though the drug-binding residues characterized are on other ribosomal components, not RPL21.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1426000","name":null,"product":"60S ribosomal protein L21","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1018600","name":null,"product":"60S ribosomal protein L21, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1332700","name":null,"product":"60S ribosomal protein L21, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPL21","evaluation":null}