{"gene":"PF3D7_1142600","run_date":"2026-09-08T14:19:05","timeline":{"discoveries":[{"year":2014,"finding":"PF3D7_1142600 (L35ae) was identified as a component of the P. falciparum 80S ribosome large subunit, as resolved in the 3.2 Å cryo-EM structure of the Pf80S ribosome bound to emetine. Its membership in the assembled 60S large subunit is established by this structural determination, but no specific mechanistic role beyond ribosomal subunit composition is described for L35ae itself.","method":"Cryo-EM structure determination at 3.2 Å resolution","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure in a single study, but no functional characterization specific to L35ae beyond its presence in the complex","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"PF3D7_1142600 (L35ae) is present as a structural component of the P. falciparum 80S ribosome large subunit, as captured in five sub-nanometer cryo-EM reconstructions of ribosomes purified from blood-stage schizonts with atomic models built by flexible fitting. No specific functional role for L35ae beyond ribosome composition is described.","method":"Cryo-EM reconstruction and atomic model building from P. falciparum schizont-stage ribosomes","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — multiple cryo-EM reconstructions in a single study establishing ribosome composition; no specific mechanistic data for L35ae","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PF3D7_1142600 (L35ae) is a structural component of the P. falciparum 80S ribosome large subunit, as resolved in the 3.2 Å cryo-EM structure of Pf80S bound to (+)-mefloquine. No specific mechanistic role for L35ae beyond ribosomal subunit membership is described.","method":"Cryo-EM structure determination at 3.2 Å resolution with site-directed mutagenesis of mefloquine-binding residues (mutations were in other ribosomal proteins, not L35ae)","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure, single study; L35ae is identified as part of the complex but is not individually characterized","pmids":["28288098"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"PF3D7_1142600 (L35ae) is a structural component of the native P. falciparum 80S ribosome in actively translating states inside infected human erythrocytes, as captured by eight high-resolution in situ cryo-electron tomography structures. No specific mechanistic role for L35ae beyond ribosomal complex membership is described.","method":"In situ cryo-electron tomography of P. falciparum-infected erythrocytes","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution in situ cryo-ET in a single study; L35ae's role is inferred only from complex membership","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1142600 (L35ae, 60S ribosomal protein L35ae) is established as a structural component of the P. falciparum 80S ribosome large (60S) subunit, as confirmed by multiple cryo-EM and cryo-ET studies at near-atomic resolution; no specific enzymatic activity, binding partner, post-translational modification, or individual functional role beyond ribosomal subunit membership has been experimentally demonstrated for this protein."},"narrative":{"mechanistic_narrative":"PF3D7_1142600 (L35ae) is a structural constituent of the large (60S) subunit of the Plasmodium falciparum 80S ribosome, established through successive high-resolution cryo-EM structures of the assembled Pf80S ribosome [PMID:24913268, PMID:28288098] and cryo-EM reconstructions of ribosomes purified from blood-stage schizonts [PMID:26432834]. Its incorporation into actively translating ribosomes within infected human erythrocytes has been directly visualized by in situ cryo-electron tomography [PMID:40825879]. Beyond this membership in the assembled 60S subunit, no enzymatic activity, individual binding partner, post-translational modification, or discrete functional role has been experimentally characterized for L35ae in the available corpus; every finding places it as one component of the ribosomal complex rather than assigning it a distinct mechanism.","teleology":[{"year":2014,"claim":"Establishing that L35ae is a bona fide component of the P. falciparum ribosome required a high-resolution structure of the assembled particle; the first such structure placed L35ae within the 60S large subunit.","evidence":"3.2 Å cryo-EM structure of the emetine-bound Pf80S ribosome","pmids":["24913268"],"confidence":"Medium","gaps":["No functional role for L35ae beyond presence in the complex","No binding partner or interface specific to L35ae defined","Structure from a single drug-bound state"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Whether L35ae is present in ribosomes from a physiologically relevant blood stage was addressed by reconstructing ribosomes purified from schizont-stage parasites, confirming its membership in the large subunit under native purification.","evidence":"Five sub-nanometer cryo-EM reconstructions with atomic models built by flexible fitting from schizont-stage ribosomes","pmids":["26432834"],"confidence":"Medium","gaps":["No mechanistic role assigned to L35ae","No stage-specific expression or regulation of L35ae shown","Contribution of L35ae to ribosome function not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"A further high-resolution structure of a drug-bound Pf80S ribosome reconfirmed L35ae as a stable structural element of the large subunit across different ligand-bound states.","evidence":"3.2 Å cryo-EM structure of Pf80S bound to (+)-mefloquine (mutagenesis targeted other ribosomal proteins, not L35ae)","pmids":["28288098"],"confidence":"Medium","gaps":["L35ae itself was not mutated or functionally probed","No interaction with the drug or catalytic centers demonstrated for L35ae"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether L35ae is incorporated into ribosomes engaged in translation in the native cellular environment was resolved by in situ imaging, confirming its presence in actively translating 80S ribosomes inside infected erythrocytes.","evidence":"Eight high-resolution in situ cryo-electron tomography structures of P. falciparum-infected human erythrocytes","pmids":["40825879"],"confidence":"Medium","gaps":["No distinct functional contribution of L35ae to translation demonstrated","No dynamics or conformational role specific to L35ae resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether L35ae has any function beyond serving as a structural component of the 60S subunit, including any binding partner, post-translational modification, or role in ribosome assembly or translational regulation specific to this protein.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genetic knockout or knockdown of L35ae reported","No L35ae-specific interaction or modification characterized","No essentiality or phenotype tied to L35ae itself"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["P. falciparum 80S ribosome large (60S) subunit"],"partners":[],"other_free_text":["L35ae has been resolved only as a structural member of the assembled Pf80S ribosome by cryo-EM and in situ cryo-ET; no function, interaction, or modification specific to this protein has been experimentally demonstrated in the corpus."]}},"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":4839,"output_tokens":1190,"usd":0.016183,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6008,"output_tokens":1929,"usd":0.039133,"stage2_stop_reason":"end_turn"},"total_usd":0.055316,"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\": \"PF3D7_1142600 (L35ae) was identified as a component of the P. falciparum 80S ribosome large subunit, as resolved in the 3.2 Å cryo-EM structure of the Pf80S ribosome bound to emetine. Its membership in the assembled 60S large subunit is established by this structural determination, but no specific mechanistic role beyond ribosomal subunit composition is described for L35ae itself.\",\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 in a single study, but no functional characterization specific to L35ae beyond its presence in the complex\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"PF3D7_1142600 (L35ae) is present as a structural component of the P. falciparum 80S ribosome large subunit, as captured in five sub-nanometer cryo-EM reconstructions of ribosomes purified from blood-stage schizonts with atomic models built by flexible fitting. No specific functional role for L35ae beyond ribosome composition is described.\",\n      \"method\": \"Cryo-EM reconstruction and atomic model building from P. falciparum schizont-stage ribosomes\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — multiple cryo-EM reconstructions in a single study establishing ribosome composition; no specific mechanistic data for L35ae\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PF3D7_1142600 (L35ae) is a structural component of the P. falciparum 80S ribosome large subunit, as resolved in the 3.2 Å cryo-EM structure of Pf80S bound to (+)-mefloquine. No specific mechanistic role for L35ae beyond ribosomal subunit membership is described.\",\n      \"method\": \"Cryo-EM structure determination at 3.2 Å resolution with site-directed mutagenesis of mefloquine-binding residues (mutations were in other ribosomal proteins, not L35ae)\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM structure, single study; L35ae is identified as part of the complex but is not individually characterized\",\n      \"pmids\": [\"28288098\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PF3D7_1142600 (L35ae) is a structural component of the native P. falciparum 80S ribosome in actively translating states inside infected human erythrocytes, as captured by eight high-resolution in situ cryo-electron tomography structures. No specific mechanistic role for L35ae beyond ribosomal complex membership is described.\",\n      \"method\": \"In situ cryo-electron tomography of P. falciparum-infected erythrocytes\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution in situ cryo-ET in a single study; L35ae's role is inferred only from complex membership\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1142600 (L35ae, 60S ribosomal protein L35ae) is established as a structural component of the P. falciparum 80S ribosome large (60S) subunit, as confirmed by multiple cryo-EM and cryo-ET studies at near-atomic resolution; no specific enzymatic activity, binding partner, post-translational modification, or individual functional role beyond ribosomal subunit membership has been experimentally demonstrated for this protein.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1142600 (L35ae) is a structural constituent of the large (60S) subunit of the Plasmodium falciparum 80S ribosome, established through successive high-resolution cryo-EM structures of the assembled Pf80S ribosome [#0, #2] and cryo-EM reconstructions of ribosomes purified from blood-stage schizonts [#1]. Its incorporation into actively translating ribosomes within infected human erythrocytes has been directly visualized by in situ cryo-electron tomography [#3]. Beyond this membership in the assembled 60S subunit, no enzymatic activity, individual binding partner, post-translational modification, or discrete functional role has been experimentally characterized for L35ae in the available corpus; every finding places it as one component of the ribosomal complex rather than assigning it a distinct mechanism.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing that L35ae is a bona fide component of the P. falciparum ribosome required a high-resolution structure of the assembled particle; the first such structure placed L35ae within the 60S large subunit.\",\n      \"evidence\": \"3.2 Å cryo-EM structure of the emetine-bound Pf80S ribosome\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional role for L35ae beyond presence in the complex\",\n        \"No binding partner or interface specific to L35ae defined\",\n        \"Structure from a single drug-bound state\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether L35ae is present in ribosomes from a physiologically relevant blood stage was addressed by reconstructing ribosomes purified from schizont-stage parasites, confirming its membership in the large subunit under native purification.\",\n      \"evidence\": \"Five sub-nanometer cryo-EM reconstructions with atomic models built by flexible fitting from schizont-stage ribosomes\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No mechanistic role assigned to L35ae\",\n        \"No stage-specific expression or regulation of L35ae shown\",\n        \"Contribution of L35ae to ribosome function not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"A further high-resolution structure of a drug-bound Pf80S ribosome reconfirmed L35ae as a stable structural element of the large subunit across different ligand-bound states.\",\n      \"evidence\": \"3.2 Å cryo-EM structure of Pf80S bound to (+)-mefloquine (mutagenesis targeted other ribosomal proteins, not L35ae)\",\n      \"pmids\": [\"28288098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"L35ae itself was not mutated or functionally probed\",\n        \"No interaction with the drug or catalytic centers demonstrated for L35ae\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether L35ae is incorporated into ribosomes engaged in translation in the native cellular environment was resolved by in situ imaging, confirming its presence in actively translating 80S ribosomes inside infected erythrocytes.\",\n      \"evidence\": \"Eight high-resolution in situ cryo-electron tomography structures of P. falciparum-infected human erythrocytes\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No distinct functional contribution of L35ae to translation demonstrated\",\n        \"No dynamics or conformational role specific to L35ae resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether L35ae has any function beyond serving as a structural component of the 60S subunit, including any binding partner, post-translational modification, or role in ribosome assembly or translational regulation specific to this protein.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No genetic knockout or knockdown of L35ae reported\",\n        \"No L35ae-specific interaction or modification characterized\",\n        \"No essentiality or phenotype tied to L35ae itself\"\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    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"P. falciparum 80S ribosome large (60S) subunit\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"L35ae has been resolved only as a structural member of the assembled Pf80S ribosome by cryo-EM and in situ cryo-ET; no function, interaction, or modification specific to this protein has been experimentally demonstrated in the corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1142600","name":null,"product":"60S ribosomal protein L35ae, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0906400","name":null,"product":"60S ribosomal protein L35ae, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0940400","name":null,"product":"60S ribosomal protein L35ae, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}