{"gene":"PF3D7_0611700","run_date":"2026-09-08T12:51:26","timeline":{"discoveries":[{"year":2014,"finding":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution was solved with emetine bound; RPL39 (PF3D7_0611700) is a structural component of the 60S large subunit of this ribosome complex as visualized in the structure.","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 ribosome composition including 60S subunit proteins, but the abstract does not describe specific functional experiments targeting RPL39 individually; 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 the structural composition of the 80S ribosome, within which RPL39 (PF3D7_0611700) resides as a 60S subunit component; atomic models were built by flexible fitting into these density maps.","method":"Cryo-EM reconstruction with flexible fitting of atomic models; ribosome purified from blood-stage schizonts","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — sub-nanometer cryo-EM with atomic model building establishes ribosome composition, but no specific functional experiment targets RPL39 individually; single study.","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 RPL39 (PF3D7_0611700) as a structural component of the 60S large subunit; mutagenesis of ribosome binding residues confirmed the ribosome as the drug target.","method":"Cryo-EM at 3.2 Å; site-directed mutagenesis of binding residues; parasite resistance assay","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM with mutagenesis confirms ribosome composition and drug target, but no specific functional experiment targets RPL39 individually; single study.","pmids":["28288098"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In situ cryo-electron tomography of P. falciparum-infected erythrocytes resolved eight high-resolution structures of the native malarial 80S ribosome in actively translating states, establishing RPL39 (PF3D7_0611700) as a structural component of the 60S subunit within the native cellular translating ribosome; inhibitor treatment revealed changes in elongation factor-bound ribosomal states and apparent upregulation of ribosome biogenesis.","method":"In situ cryo-electron tomography inside infected erythrocytes; high-resolution structural determination of native translating ribosomes","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in situ cryo-ET at high resolution within native cellular context is rigorous for ribosome composition, but no specific functional experiment targets RPL39 individually; single study.","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"RPL39 (PF3D7_0611700) is established as a structural component of the 60S large subunit of the P. falciparum 80S cytoplasmic ribosome, as confirmed by multiple high-resolution cryo-EM and in situ cryo-ET structures of the native translating malarial ribosome; no specific functional or enzymatic role has been assigned to RPL39 beyond its membership in this complex."},"narrative":{"mechanistic_narrative":"RPL39 (PF3D7_0611700) is a structural component of the 60S large subunit of the Plasmodium falciparum 80S cytoplasmic ribosome, resolved as part of the assembled particle across multiple high-resolution cryo-EM structures [PMID:24913268, PMID:28288098] and, most recently, within the native translating ribosome imaged in situ by cryo-electron tomography inside infected erythrocytes [PMID:40825879]. Its presence in the 60S subunit is consistent across ribosomes purified from blood-stage schizonts and within actively translating states in the cellular context [PMID:26432834, PMID:40825879]. Beyond its membership in the 60S large subunit of the malarial ribosome, no specific functional, enzymatic, or regulatory role has been assigned to RPL39 (PF3D7_0611700) in the available corpus; the structural studies that resolve it are directed at the ribosome as a whole and as a drug target rather than at this protein individually [PMID:24913268, PMID:28288098, PMID:40825879].","teleology":[{"year":2014,"claim":"The first atomic-resolution view of the malarial ribosome was needed to define its protein composition; this established RPL39 as a resolved constituent of the 60S large subunit.","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 targets RPL39 individually","No role beyond structural membership in the 60S subunit is defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Whether the ribosome composition held in physiologically relevant blood-stage parasites was open; sub-nanometer reconstructions from schizont ribosomes confirmed RPL39 as a 60S component in native blood-stage ribosomes.","evidence":"Cryo-EM reconstruction with flexible fitting of atomic models from blood-stage schizont ribosomes","pmids":["26432834"],"confidence":"Medium","gaps":["No individual functional assay on RPL39","Interactions or assembly role of RPL39 within the 60S not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Structural characterization in the context of antimalarial drug binding tested whether the ribosome is the drug target; RPL39 was again resolved as part of the 60S subunit, with mutagenesis confirming the ribosome as the target.","evidence":"Cryo-EM at 3.2 Å with mefloquine bound, plus site-directed mutagenesis and parasite resistance assay","pmids":["28288098"],"confidence":"Medium","gaps":["Drug-target validation concerns the ribosome, not RPL39 specifically","No evidence RPL39 contributes to drug binding or resistance"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether the composition observed in purified ribosomes reflects the native translating ribosome in cells was unresolved; in situ cryo-ET placed RPL39 within the 60S subunit of actively translating ribosomes inside infected erythrocytes.","evidence":"In situ cryo-electron tomography of native translating ribosomes within P. falciparum-infected erythrocytes","pmids":["40825879"],"confidence":"Medium","gaps":["Elongation-state and biogenesis changes were observed for the ribosome, not attributed to RPL39","No functional dependency of translation on RPL39 established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether RPL39 has any function beyond serving as a 60S structural subunit — in ribosome assembly, translation fidelity, or drug interaction — remains uncharacterized in the available corpus.","evidence":"No discovery targets RPL39 individually by knockdown, mutation, or biochemical assay","pmids":[],"confidence":"Medium","gaps":["No genetic or biochemical perturbation of RPL39 reported","No specific molecular activity assigned to RPL39","No interaction partners specific to RPL39 defined beyond the ribosome"],"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":["RPL39 (PF3D7_0611700) is established only as a structural constituent of the 60S large subunit; no function is assigned to it beyond membership in this complex.","Drug-target validation and elongation/biogenesis observations in the cited structures concern the ribosome as a whole, not RPL39 individually."]}},"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":1189,"usd":0.016171,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6020,"output_tokens":2040,"usd":0.04055,"stage2_stop_reason":"end_turn"},"total_usd":0.056721,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","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 solved with emetine bound; RPL39 (PF3D7_0611700) is a structural component of the 60S large subunit of this ribosome complex as visualized in the structure.\",\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 ribosome composition including 60S subunit proteins, but the abstract does not describe specific functional experiments targeting RPL39 individually; 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 the structural composition of the 80S ribosome, within which RPL39 (PF3D7_0611700) resides as a 60S subunit component; atomic models were built by flexible fitting into these density maps.\",\n      \"method\": \"Cryo-EM reconstruction with flexible fitting of atomic models; ribosome purified from blood-stage schizonts\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — sub-nanometer cryo-EM with atomic model building establishes ribosome composition, but no specific functional experiment targets RPL39 individually; single study.\",\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 RPL39 (PF3D7_0611700) as a structural component of the 60S large subunit; mutagenesis of ribosome binding residues confirmed the ribosome as the drug target.\",\n      \"method\": \"Cryo-EM at 3.2 Å; site-directed mutagenesis of binding residues; parasite resistance assay\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM with mutagenesis confirms ribosome composition and drug target, but no specific functional experiment targets RPL39 individually; 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 P. falciparum-infected erythrocytes resolved eight high-resolution structures of the native malarial 80S ribosome in actively translating states, establishing RPL39 (PF3D7_0611700) as a structural component of the 60S subunit within the native cellular translating ribosome; inhibitor treatment revealed changes in elongation factor-bound ribosomal states and apparent upregulation of ribosome biogenesis.\",\n      \"method\": \"In situ cryo-electron tomography inside infected erythrocytes; high-resolution structural determination of native translating ribosomes\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in situ cryo-ET at high resolution within native cellular context is rigorous for ribosome composition, but no specific functional experiment targets RPL39 individually; single study.\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"RPL39 (PF3D7_0611700) is established as a structural component of the 60S large subunit of the P. falciparum 80S cytoplasmic ribosome, as confirmed by multiple high-resolution cryo-EM and in situ cryo-ET structures of the native translating malarial ribosome; no specific functional or enzymatic role has been assigned to RPL39 beyond its membership in this complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPL39 (PF3D7_0611700) is a structural component of the 60S large subunit of the Plasmodium falciparum 80S cytoplasmic ribosome, resolved as part of the assembled particle across multiple high-resolution cryo-EM structures [#0, #2] and, most recently, within the native translating ribosome imaged in situ by cryo-electron tomography inside infected erythrocytes [#3]. Its presence in the 60S subunit is consistent across ribosomes purified from blood-stage schizonts and within actively translating states in the cellular context [#1, #3]. Beyond its membership in the 60S large subunit of the malarial ribosome, no specific functional, enzymatic, or regulatory role has been assigned to RPL39 (PF3D7_0611700) in the available corpus; the structural studies that resolve it are directed at the ribosome as a whole and as a drug target rather than at this protein individually [#0, #2, #3].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"The first atomic-resolution view of the malarial ribosome was needed to define its protein composition; this established RPL39 as a resolved constituent of the 60S large subunit.\",\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 targets RPL39 individually\",\n        \"No role beyond structural membership in the 60S subunit is defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether the ribosome composition held in physiologically relevant blood-stage parasites was open; sub-nanometer reconstructions from schizont ribosomes confirmed RPL39 as a 60S component in native blood-stage ribosomes.\",\n      \"evidence\": \"Cryo-EM reconstruction with flexible fitting of atomic models from blood-stage schizont ribosomes\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No individual functional assay on RPL39\",\n        \"Interactions or assembly role of RPL39 within the 60S not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Structural characterization in the context of antimalarial drug binding tested whether the ribosome is the drug target; RPL39 was again resolved as part of the 60S subunit, with mutagenesis confirming the ribosome as the target.\",\n      \"evidence\": \"Cryo-EM at 3.2 Å with mefloquine bound, plus site-directed mutagenesis and parasite resistance assay\",\n      \"pmids\": [\"28288098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Drug-target validation concerns the ribosome, not RPL39 specifically\",\n        \"No evidence RPL39 contributes to drug binding or resistance\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether the composition observed in purified ribosomes reflects the native translating ribosome in cells was unresolved; in situ cryo-ET placed RPL39 within the 60S subunit of actively translating ribosomes inside infected erythrocytes.\",\n      \"evidence\": \"In situ cryo-electron tomography of native translating ribosomes within P. falciparum-infected erythrocytes\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Elongation-state and biogenesis changes were observed for the ribosome, not attributed to RPL39\",\n        \"No functional dependency of translation on RPL39 established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether RPL39 has any function beyond serving as a 60S structural subunit — in ribosome assembly, translation fidelity, or drug interaction — remains uncharacterized in the available corpus.\",\n      \"evidence\": \"No discovery targets RPL39 individually by knockdown, mutation, or biochemical assay\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No genetic or biochemical perturbation of RPL39 reported\",\n        \"No specific molecular activity assigned to RPL39\",\n        \"No interaction partners specific to RPL39 defined beyond the ribosome\"\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\": [3]}\n    ],\n    \"complexes\": [\n      \"60S large ribosomal subunit of the P. falciparum 80S cytoplasmic ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"RPL39 (PF3D7_0611700) is established only as a structural constituent of the 60S large subunit; no function is assigned to it beyond membership in this complex.\",\n      \"Drug-target validation and elongation/biogenesis observations in the cited structures concern the ribosome as a whole, not RPL39 individually.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0611700","name":null,"product":"60S ribosomal protein L39","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0110000","name":null,"product":"60S ribosomal protein L39, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1138400","name":null,"product":"60S ribosomal protein L39, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPL39","evaluation":null}