{"gene":"PF3D7_1365900","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, revealing the structural context of the large ribosomal subunit including 60S components such as L40 (PF3D7_1365900) as part of the ribosomal architecture. However, no specific mechanistic finding about L40/PF3D7_1365900 individually was reported beyond its membership in the 60S ribosomal subunit.","method":"Cryo-EM structure determination at 3.2 Å resolution","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 2 / Weak — high-resolution structure of the whole ribosome complex; no specific functional or mechanistic data reported for L40/PF3D7_1365900 individually","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In situ cryo-electron tomography structures of the native P. falciparum 80S ribosome in actively translating states were determined inside infected erythrocytes, placing L40 (PF3D7_1365900) as a structural component of the 60S subunit within the physiologically active ribosome. No specific mechanistic finding about L40 individually beyond its membership in the ribosomal complex was reported.","method":"In situ cryo-electron tomography; eight high-resolution structures of the native ribosome in translating states","journal":"Nature structural & molecular biology","confidence":"Low","confidence_rationale":"Tier 2 / Weak — high-resolution in situ structural work on the whole ribosome; no specific functional data reported for L40/PF3D7_1365900 individually","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1365900 (L40, ubiquitin-60S ribosomal protein L40) is established as a structural component of the P. falciparum 60S ribosomal subunit within the 80S ribosome, as visualized by high-resolution cryo-EM and in situ cryo-electron tomography, but no specific mechanistic role distinct from its membership in the ribosomal complex has been experimentally characterized in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_1365900 (L40) is a structural component of the 60S large subunit of the P. falciparum 80S ribosome, resolved within the ribosomal architecture by 3.2 Å cryo-EM [PMID:24913268] and placed within the natively translating ribosome by in situ cryo-electron tomography inside infected erythrocytes [PMID:40825879]. Beyond this membership in the 60S ribosomal subunit, no mechanistic role for L40/PF3D7_1365900 distinct from the ribosomal complex has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"The structural context of the P. falciparum large ribosomal subunit was undefined at high resolution; solving the 80S ribosome established where 60S components including L40 sit within the ribosomal architecture.","evidence":"Cryo-EM structure determination of the P. falciparum 80S ribosome at 3.2 Å resolution","pmids":["24913268"],"confidence":"Low","gaps":["No functional or mechanistic role assigned to L40/PF3D7_1365900 individually beyond membership in the 60S subunit","Ribosome was not captured in an actively translating state","No test of whether L40 is essential or has an extra-ribosomal function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether L40 occupies its ribosomal position in the physiologically active, translating ribosome in vivo was unresolved; in situ tomography confirmed its placement within the native 60S subunit during translation inside infected erythrocytes.","evidence":"In situ cryo-electron tomography yielding eight high-resolution structures of the native ribosome in translating states within infected erythrocytes","pmids":["40825879"],"confidence":"Low","gaps":["No specific mechanistic function reported for L40 individually beyond ribosomal membership","No evidence addressing an independent role for the ubiquitin moiety fused to L40","No essentiality or perturbation data for L40 in P. falciparum"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether L40/PF3D7_1365900 has any function distinct from its structural role in the 60S ribosomal subunit — including any role of its ubiquitin fusion component — remains uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No biochemical, genetic, or functional assay specific to L40 exists in the corpus","The role of the ubiquitin domain (co-translational processing, ribosome biogenesis) has not been examined","No interaction partners beyond the ribosome established for L40 itself"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["60S large ribosomal subunit of the P. falciparum 80S ribosome"],"partners":[],"other_free_text":["Established only as a structural constituent of the 60S ribosomal subunit; no mechanistic role distinct from ribosomal membership has been characterized for PF3D7_1365900 in the available corpus.","All evidence is from P. falciparum whole-ribosome structural studies (cryo-EM and in situ cryo-ET); no L40-specific functional experiments are present."]}},"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":"20078859","id":"PMC_20078859","title":"Assessing functional annotation transfers with inter-species conserved coexpression: application to Plasmodium falciparum.","date":"2010","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/20078859","citation_count":12,"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":5354,"output_tokens":687,"usd":0.013184,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5275,"output_tokens":1441,"usd":0.0312,"stage2_stop_reason":"end_turn"},"total_usd":0.044384,"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, revealing the structural context of the large ribosomal subunit including 60S components such as L40 (PF3D7_1365900) as part of the ribosomal architecture. However, no specific mechanistic finding about L40/PF3D7_1365900 individually was reported beyond its membership in the 60S ribosomal subunit.\",\n      \"method\": \"Cryo-EM structure determination at 3.2 Å resolution\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — high-resolution structure of the whole ribosome complex; no specific functional or mechanistic data reported for L40/PF3D7_1365900 individually\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In situ cryo-electron tomography structures of the native P. falciparum 80S ribosome in actively translating states were determined inside infected erythrocytes, placing L40 (PF3D7_1365900) as a structural component of the 60S subunit within the physiologically active ribosome. No specific mechanistic finding about L40 individually beyond its membership in the ribosomal complex was reported.\",\n      \"method\": \"In situ cryo-electron tomography; eight high-resolution structures of the native ribosome in translating states\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — high-resolution in situ structural work on the whole ribosome; no specific functional data reported for L40/PF3D7_1365900 individually\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1365900 (L40, ubiquitin-60S ribosomal protein L40) is established as a structural component of the P. falciparum 60S ribosomal subunit within the 80S ribosome, as visualized by high-resolution cryo-EM and in situ cryo-electron tomography, but no specific mechanistic role distinct from its membership in the ribosomal complex has been experimentally characterized in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1365900 (L40) is a structural component of the 60S large subunit of the P. falciparum 80S ribosome, resolved within the ribosomal architecture by 3.2 Å cryo-EM [#0] and placed within the natively translating ribosome by in situ cryo-electron tomography inside infected erythrocytes [#1]. Beyond this membership in the 60S ribosomal subunit, no mechanistic role for L40/PF3D7_1365900 distinct from the ribosomal complex has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"The structural context of the P. falciparum large ribosomal subunit was undefined at high resolution; solving the 80S ribosome established where 60S components including L40 sit within the ribosomal architecture.\",\n      \"evidence\": \"Cryo-EM structure determination of the P. falciparum 80S ribosome at 3.2 Å resolution\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No functional or mechanistic role assigned to L40/PF3D7_1365900 individually beyond membership in the 60S subunit\",\n        \"Ribosome was not captured in an actively translating state\",\n        \"No test of whether L40 is essential or has an extra-ribosomal function\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether L40 occupies its ribosomal position in the physiologically active, translating ribosome in vivo was unresolved; in situ tomography confirmed its placement within the native 60S subunit during translation inside infected erythrocytes.\",\n      \"evidence\": \"In situ cryo-electron tomography yielding eight high-resolution structures of the native ribosome in translating states within infected erythrocytes\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No specific mechanistic function reported for L40 individually beyond ribosomal membership\",\n        \"No evidence addressing an independent role for the ubiquitin moiety fused to L40\",\n        \"No essentiality or perturbation data for L40 in P. falciparum\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether L40/PF3D7_1365900 has any function distinct from its structural role in the 60S ribosomal subunit — including any role of its ubiquitin fusion component — remains uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No biochemical, genetic, or functional assay specific to L40 exists in the corpus\",\n        \"The role of the ubiquitin domain (co-translational processing, ribosome biogenesis) has not been examined\",\n        \"No interaction partners beyond the ribosome established for L40 itself\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003735\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0022625\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"60S large ribosomal subunit of the P. falciparum 80S ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Established only as a structural constituent of the 60S ribosomal subunit; no mechanistic role distinct from ribosomal membership has been characterized for PF3D7_1365900 in the available corpus.\",\n      \"All evidence is from P. falciparum whole-ribosome structural studies (cryo-EM and in situ cryo-ET); no L40-specific functional experiments are present.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1365900","name":null,"product":"ubiquitin-60S ribosomal protein L40","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1141700","name":null,"product":"ubiquitin-60S ribosomal protein L40, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1105400","name":null,"product":"ubiquitin-60S ribosomal protein L40, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}