{"gene":"PF3D7_1341200","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2014,"finding":"The cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution was solved with emetine bound; L18 (PF3D7_1341200), as a constituent 60S ribosomal protein, is structurally resolved as part of the large subunit of this ribosome complex.","method":"Cryo-EM structure determination at 3.2 Å resolution","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure of the whole ribosome establishes L18 membership in the 60S subunit complex, but no functional experiment specifically interrogates L18 itself; single study.","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Five cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts were determined at sub-nanometer resolution and atomic models were built; L18 (PF3D7_1341200) is a structural component of the 60S large subunit in these ribosome assemblies. Structural and dynamic features distinguishing the P. falciparum ribosome from mammalian ribosomes were identified.","method":"Cryo-EM with flexible-fitting atomic model building; ribosome purification from blood-stage schizonts","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — multiple cryo-EM reconstructions establish ribosome architecture including the 60S subunit where L18 resides, but no experiment specifically addresses L18 function or interactions independently.","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"A 3.2 Å cryo-EM structure of the P. falciparum 80S ribosome bound to (+)-mefloquine was solved; L18 (PF3D7_1341200), as a constituent 60S large-subunit protein, is present in this structurally characterized ribosome complex. Mefloquine binds the GTPase-associated centre of the large subunit, and mutagenesis of binding-site residues confers resistance, confirming the ribosome as the drug target.","method":"Cryo-EM at 3.2 Å; site-directed mutagenesis of mefloquine-binding residues; parasite growth assays","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — rigorous structural and mutagenesis work on the ribosome complex; L18 membership in the 60S subunit is incidentally established but no experiment specifically interrogates L18.","pmids":["28288098"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Eight high-resolution structures of the native P. falciparum ribosome in actively translating states were determined by in situ cryo-electron tomography inside infected human erythrocytes; L18 (PF3D7_1341200) is a component of the 60S large subunit present in these native, physiologically translating ribosome complexes. Treatment with a Plasmodium-specific translation inhibitor decreased elongation factor-bound ribosomal states and appeared to upregulate ribosome biogenesis.","method":"In situ cryo-electron tomography inside P. falciparum-infected human erythrocytes; integrated structural biology approach","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — sophisticated in-cell structural method establishes the native ribosome architecture (including 60S subunit with L18) during active translation, but no experiment specifically addresses L18 itself.","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1341200 (L18) is established as a structural component of the 60S large subunit of the P. falciparum 80S cytoplasmic ribosome, as evidenced by multiple high-resolution cryo-EM and cryo-ET structures of the ribosome complex; no experiment has specifically interrogated the function, interactions, or modifications of L18 itself beyond its presence in this complex."},"narrative":{"mechanistic_narrative":"PF3D7_1341200 (L18) is a structural constituent of the 60S large subunit of the Plasmodium falciparum 80S cytoplasmic ribosome, identified within the large subunit in multiple high-resolution cryo-EM structures of the intact ribosome [PMID:24913268, PMID:26432834]. It is present in ribosomes purified from blood-stage schizonts [PMID:26432834] and in native, actively translating ribosomes imaged in situ inside infected human erythrocytes by cryo-electron tomography [PMID:40825879]. Beyond its membership in the 60S subunit as resolved in these whole-ribosome structures, no experiment in the available corpus has specifically interrogated the function, interactions, or modifications of L18 itself; the structures that establish its position also identified antimalarial drug-binding sites (emetine, mefloquine) on the ribosome, but these bind other regions of the large subunit rather than L18 [PMID:24913268, PMID:28288098]. The corpus establishes nothing about PF3D7_1341200 beyond its role as a component of the 60S ribosomal large subunit.","teleology":[{"year":2014,"claim":"Establishing the architecture of the P. falciparum 80S ribosome placed L18 within the resolved 60S large subunit, defining its identity as a structural ribosomal protein of the parasite.","evidence":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å with emetine bound","pmids":["24913268"],"confidence":"Medium","gaps":["No functional experiment interrogates L18 independently of the ribosome complex","No specific interactions or modifications of L18 defined","Drug-binding characterized for the ribosome, not for L18"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Multiple cryo-EM reconstructions of schizont-derived ribosomes confirmed L18 as a stable 60S component and distinguished parasite ribosome features from mammalian ribosomes, relevant for selective targeting.","evidence":"Five sub-nanometer cryo-EM reconstructions with flexible-fitting atomic models from blood-stage schizont ribosomes","pmids":["26432834"],"confidence":"Medium","gaps":["L18-specific structural or sequence divergence from mammalian counterpart not isolated","No functional assay of L18","Role of L18 in translation dynamics not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"A drug-bound ribosome structure validated the 60S subunit as an antimalarial target while incidentally confirming L18 membership, without implicating L18 in the drug-binding mechanism.","evidence":"Cryo-EM at 3.2 Å of the ribosome bound to (+)-mefloquine, with mutagenesis of binding-site residues and parasite growth assays","pmids":["28288098"],"confidence":"Medium","gaps":["Mefloquine binds the GTPase-associated centre, not L18","No evidence L18 contributes to drug binding or resistance","L18 function untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"In-cell structural imaging placed L18 within native, actively translating ribosomes, confirming it participates in functional ribosomes under physiological conditions rather than only in purified preparations.","evidence":"In situ cryo-electron tomography of eight translating ribosome states inside infected human erythrocytes, with a Plasmodium-specific translation inhibitor","pmids":["40825879"],"confidence":"Medium","gaps":["L18-specific behavior across translation states not resolved","No perturbation of L18 to test its functional contribution","L18 role in ribosome biogenesis response not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether L18 has any function, interaction, or modification beyond serving as a structural 60S component remains entirely uncharacterized in the available corpus.","evidence":"No study specifically interrogates PF3D7_1341200 apart from whole-ribosome structural work","pmids":[],"confidence":"Medium","gaps":["No genetic knockout or knockdown of L18","No L18-specific interaction or modification mapping","No assay separating L18 from the intact ribosome complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["60S large ribosomal subunit of the P. falciparum 80S cytoplasmic ribosome"],"partners":[],"other_free_text":["L18 is resolved only as a structural constituent within whole-ribosome cryo-EM/cryo-ET structures; no L18-specific function, interaction, or modification has been experimentally interrogated.","Antimalarial drug-binding sites (emetine, mefloquine) characterized in these structures map to other regions of the large subunit, not to L18."]}},"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":272,"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":136,"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":45,"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":7,"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":3,"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":4837,"output_tokens":1274,"usd":0.01681,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6123,"output_tokens":2118,"usd":0.041783,"stage2_stop_reason":"end_turn"},"total_usd":0.058593,"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\": \"The cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution was solved with emetine bound; L18 (PF3D7_1341200), as a constituent 60S ribosomal protein, is structurally resolved as part of the large subunit of this ribosome complex.\",\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 of the whole ribosome establishes L18 membership in the 60S subunit complex, but no functional experiment specifically interrogates L18 itself; single study.\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Five cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts were determined at sub-nanometer resolution and atomic models were built; L18 (PF3D7_1341200) is a structural component of the 60S large subunit in these ribosome assemblies. Structural and dynamic features distinguishing the P. falciparum ribosome from mammalian ribosomes were identified.\",\n      \"method\": \"Cryo-EM with flexible-fitting atomic model building; ribosome purification from blood-stage schizonts\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — multiple cryo-EM reconstructions establish ribosome architecture including the 60S subunit where L18 resides, but no experiment specifically addresses L18 function or interactions independently.\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"A 3.2 Å cryo-EM structure of the P. falciparum 80S ribosome bound to (+)-mefloquine was solved; L18 (PF3D7_1341200), as a constituent 60S large-subunit protein, is present in this structurally characterized ribosome complex. Mefloquine binds the GTPase-associated centre of the large subunit, and mutagenesis of binding-site residues confers resistance, confirming the ribosome as the drug target.\",\n      \"method\": \"Cryo-EM at 3.2 Å; site-directed mutagenesis of mefloquine-binding residues; parasite growth assays\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — rigorous structural and mutagenesis work on the ribosome complex; L18 membership in the 60S subunit is incidentally established but no experiment specifically interrogates L18.\",\n      \"pmids\": [\"28288098\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Eight high-resolution structures of the native P. falciparum ribosome in actively translating states were determined by in situ cryo-electron tomography inside infected human erythrocytes; L18 (PF3D7_1341200) is a component of the 60S large subunit present in these native, physiologically translating ribosome complexes. Treatment with a Plasmodium-specific translation inhibitor decreased elongation factor-bound ribosomal states and appeared to upregulate ribosome biogenesis.\",\n      \"method\": \"In situ cryo-electron tomography inside P. falciparum-infected human erythrocytes; integrated structural biology approach\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — sophisticated in-cell structural method establishes the native ribosome architecture (including 60S subunit with L18) during active translation, but no experiment specifically addresses L18 itself.\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1341200 (L18) is established as a structural component of the 60S large subunit of the P. falciparum 80S cytoplasmic ribosome, as evidenced by multiple high-resolution cryo-EM and cryo-ET structures of the ribosome complex; no experiment has specifically interrogated the function, interactions, or modifications of L18 itself beyond its presence in this complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1341200 (L18) is a structural constituent of the 60S large subunit of the Plasmodium falciparum 80S cytoplasmic ribosome, identified within the large subunit in multiple high-resolution cryo-EM structures of the intact ribosome [#0, #1]. It is present in ribosomes purified from blood-stage schizonts [#1] and in native, actively translating ribosomes imaged in situ inside infected human erythrocytes by cryo-electron tomography [#3]. Beyond its membership in the 60S subunit as resolved in these whole-ribosome structures, no experiment in the available corpus has specifically interrogated the function, interactions, or modifications of L18 itself; the structures that establish its position also identified antimalarial drug-binding sites (emetine, mefloquine) on the ribosome, but these bind other regions of the large subunit rather than L18 [#0, #2]. The corpus establishes nothing about PF3D7_1341200 beyond its role as a component of the 60S ribosomal large subunit.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing the architecture of the P. falciparum 80S ribosome placed L18 within the resolved 60S large subunit, defining its identity as a structural ribosomal protein of the parasite.\",\n      \"evidence\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å with emetine bound\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional experiment interrogates L18 independently of the ribosome complex\",\n        \"No specific interactions or modifications of L18 defined\",\n        \"Drug-binding characterized for the ribosome, not for L18\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Multiple cryo-EM reconstructions of schizont-derived ribosomes confirmed L18 as a stable 60S component and distinguished parasite ribosome features from mammalian ribosomes, relevant for selective targeting.\",\n      \"evidence\": \"Five sub-nanometer cryo-EM reconstructions with flexible-fitting atomic models from blood-stage schizont ribosomes\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"L18-specific structural or sequence divergence from mammalian counterpart not isolated\",\n        \"No functional assay of L18\",\n        \"Role of L18 in translation dynamics not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"A drug-bound ribosome structure validated the 60S subunit as an antimalarial target while incidentally confirming L18 membership, without implicating L18 in the drug-binding mechanism.\",\n      \"evidence\": \"Cryo-EM at 3.2 Å of the ribosome bound to (+)-mefloquine, with mutagenesis of binding-site residues and parasite growth assays\",\n      \"pmids\": [\"28288098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mefloquine binds the GTPase-associated centre, not L18\",\n        \"No evidence L18 contributes to drug binding or resistance\",\n        \"L18 function untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"In-cell structural imaging placed L18 within native, actively translating ribosomes, confirming it participates in functional ribosomes under physiological conditions rather than only in purified preparations.\",\n      \"evidence\": \"In situ cryo-electron tomography of eight translating ribosome states inside infected human erythrocytes, with a Plasmodium-specific translation inhibitor\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"L18-specific behavior across translation states not resolved\",\n        \"No perturbation of L18 to test its functional contribution\",\n        \"L18 role in ribosome biogenesis response not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether L18 has any function, interaction, or modification beyond serving as a structural 60S component remains entirely uncharacterized in the available corpus.\",\n      \"evidence\": \"No study specifically interrogates PF3D7_1341200 apart from whole-ribosome structural work\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No genetic knockout or knockdown of L18\",\n        \"No L18-specific interaction or modification mapping\",\n        \"No assay separating L18 from the intact 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, 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\": [3]}\n    ],\n    \"complexes\": [\n      \"60S large ribosomal subunit of the P. falciparum 80S cytoplasmic ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"L18 is resolved only as a structural constituent within whole-ribosome cryo-EM/cryo-ET structures; no L18-specific function, interaction, or modification has been experimentally interrogated.\",\n      \"Antimalarial drug-binding sites (emetine, mefloquine) characterized in these structures map to other regions of the large subunit, not to L18.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1341200","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"uncited_synthesis","uniprot_band":"empty","rules_fired":"R8","issue":"R8: 1/3 claims uncited (33%)"},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1341200","name":null,"product":"60S ribosomal protein L18, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1354400","name":null,"product":"60S ribosomal protein L18, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1260200","name":null,"product":"60S ribosomal subunit protein L18, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}