{"gene":"PF3D7_1408600","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 revealed the molecular architecture of the small subunit, in which S8e (PF3D7_1408600) is present as a component, and established the E-site of the small subunit as the binding site for emetine, which blocks mRNA/tRNA translocation.","method":"Cryo-EM structure determination at 3.2 Å resolution of the P. falciparum 80S ribosome in complex with emetine","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure establishes complex membership for S8e, but no specific functional experiment was performed on S8e itself; only its presence in the ribosome complex is inferred from the structure","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 at sub-nanometer resolution revealed structural features of the ribosome, confirming S8e (PF3D7_1408600) as a component of the small subunit, and identified structural differences from mammalian ribosomes.","method":"Cryo-EM reconstruction and atomic model building by flexible fitting from P. falciparum blood-stage schizont ribosomes","journal":"Nucleic acids research","confidence":"Low","confidence_rationale":"Tier 1 / Weak — cryo-EM structures establish ribosome composition including S8e membership, but no experiment specifically interrogates S8e function or interactions","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In situ cryo-electron tomography of actively translating P. falciparum ribosomes inside infected erythrocytes determined eight high-resolution structures of the native malarial ribosome in elongation states, establishing S8e (PF3D7_1408600) as a component of the small subunit in the physiological translation context and revealing new molecular details of the elongation cycle.","method":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; high-resolution structural determination of native translating ribosomes","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — highest-resolution in situ ribosome structures confirm small subunit composition including S8e, but no experiment specifically interrogates S8e's individual function","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1408600 (S8e) is established as a component of the P. falciparum 40S ribosomal small subunit, as confirmed by multiple cryo-EM and in situ cryo-ET structures of the Pf80S ribosome; no specific enzymatic activity, binding partner, post-translational modification, or individual functional role has been experimentally attributed to S8e beyond its membership in the ribosomal small subunit complex."},"narrative":{"mechanistic_narrative":"PF3D7_1408600 (S8e) is a constituent protein of the small (40S) subunit of the Plasmodium falciparum 80S ribosome, established solely through structural biology [PMID:24913268, PMID:40825879]. High-resolution cryo-EM of the Pf80S ribosome placed S8e within the small subunit architecture [PMID:24913268], subsequent cryo-EM reconstructions of blood-stage schizont ribosomes confirmed its presence and helped delineate structural differences from mammalian ribosomes [PMID:26432834], and in situ cryo-electron tomography of actively translating ribosomes inside infected erythrocytes established S8e as a small-subunit component in the physiological translation context during elongation [PMID:40825879]. Beyond this membership in the 40S subunit, no specific enzymatic activity, binding partner, post-translational modification, or individual functional role has been experimentally attributed to S8e in the available corpus.","teleology":[{"year":2014,"claim":"Before any structure of the malarial ribosome, the composition and molecular architecture of the P. falciparum small subunit were undefined; the first high-resolution cryo-EM structure resolved the subunit and placed S8e within it, establishing S8e as a bona fide small-subunit component.","evidence":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å in complex with emetine","pmids":["24913268"],"confidence":"Medium","gaps":["No functional experiment interrogates S8e itself; only its presence in the complex is inferred from the structure","No binding partner, PTM, or enzymatic role assigned to S8e specifically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To test whether the ribosome architecture holds in natively purified particles and how it diverges from the host, cryo-EM reconstructions from blood-stage schizonts confirmed S8e as a small-subunit component and identified structural differences from mammalian ribosomes.","evidence":"Five sub-nanometer cryo-EM reconstructions with atomic model building by flexible fitting from P. falciparum schizont ribosomes","pmids":["26432834"],"confidence":"Low","gaps":["Establishes composition only; no experiment interrogates S8e function or interactions","Does not localize S8e-specific structural divergences from the host protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"To determine whether S8e is part of the ribosome under physiological translation rather than only in purified particles, in situ cryo-ET of actively translating ribosomes inside infected erythrocytes confirmed S8e in the small subunit across elongation states.","evidence":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes yielding eight high-resolution structures of native translating ribosomes","pmids":["40825879"],"confidence":"Medium","gaps":["No experiment isolates the contribution of S8e to elongation","No functional or interaction data specific to S8e"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether S8e has any function, interaction, or regulatory role beyond its structural membership in the 40S subunit, and whether it is dispensable or essential in P. falciparum.","evidence":"No functional, genetic, or biochemical experiment on S8e is present in the corpus","pmids":[],"confidence":"Low","gaps":["No genetic knockout/knockdown data for S8e","No binding partners or PTMs identified","No S8e-specific role in translation initiation, elongation, or subunit assembly established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["40S small ribosomal subunit of the P. falciparum 80S ribosome"],"partners":[],"other_free_text":["S8e is known only as a structural component of the P. falciparum 40S ribosomal small subunit; no individual function, binding partner, PTM, or enzymatic activity has been experimentally attributed to it in the corpus.","Structural characterization spans purified 80S ribosomes (cryo-EM) and native translating ribosomes inside infected erythrocytes (in situ cryo-ET)."]}},"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":"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":4455,"output_tokens":959,"usd":0.013875,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5658,"output_tokens":1840,"usd":0.037145,"stage2_stop_reason":"end_turn"},"total_usd":0.05102,"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 revealed the molecular architecture of the small subunit, in which S8e (PF3D7_1408600) is present as a component, and established the E-site of the small subunit as the binding site for emetine, which blocks mRNA/tRNA translocation.\",\n      \"method\": \"Cryo-EM structure determination at 3.2 Å resolution of the P. falciparum 80S ribosome in complex with emetine\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM structure establishes complex membership for S8e, but no specific functional experiment was performed on S8e itself; only its presence in the ribosome complex is inferred from the structure\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Five cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts at sub-nanometer resolution revealed structural features of the ribosome, confirming S8e (PF3D7_1408600) as a component of the small subunit, and identified structural differences from mammalian ribosomes.\",\n      \"method\": \"Cryo-EM reconstruction and atomic model building by flexible fitting from P. falciparum blood-stage schizont ribosomes\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 1 / Weak — cryo-EM structures establish ribosome composition including S8e membership, but no experiment specifically interrogates S8e function or interactions\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In situ cryo-electron tomography of actively translating P. falciparum ribosomes inside infected erythrocytes determined eight high-resolution structures of the native malarial ribosome in elongation states, establishing S8e (PF3D7_1408600) as a component of the small subunit in the physiological translation context and revealing new molecular details of the elongation cycle.\",\n      \"method\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; high-resolution structural determination of native translating ribosomes\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — highest-resolution in situ ribosome structures confirm small subunit composition including S8e, but no experiment specifically interrogates S8e's individual function\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1408600 (S8e) is established as a component of the P. falciparum 40S ribosomal small subunit, as confirmed by multiple cryo-EM and in situ cryo-ET structures of the Pf80S ribosome; no specific enzymatic activity, binding partner, post-translational modification, or individual functional role has been experimentally attributed to S8e beyond its membership in the ribosomal small subunit complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1408600 (S8e) is a constituent protein of the small (40S) subunit of the Plasmodium falciparum 80S ribosome, established solely through structural biology [#0, #2]. High-resolution cryo-EM of the Pf80S ribosome placed S8e within the small subunit architecture [#0], subsequent cryo-EM reconstructions of blood-stage schizont ribosomes confirmed its presence and helped delineate structural differences from mammalian ribosomes [#1], and in situ cryo-electron tomography of actively translating ribosomes inside infected erythrocytes established S8e as a small-subunit component in the physiological translation context during elongation [#2]. Beyond this membership in the 40S subunit, no specific enzymatic activity, binding partner, post-translational modification, or individual functional role has been experimentally attributed to S8e in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Before any structure of the malarial ribosome, the composition and molecular architecture of the P. falciparum small subunit were undefined; the first high-resolution cryo-EM structure resolved the subunit and placed S8e within it, establishing S8e as a bona fide small-subunit component.\",\n      \"evidence\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å in complex with emetine\",\n      \"pmids\": [\n        \"24913268\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional experiment interrogates S8e itself; only its presence in the complex is inferred from the structure\",\n        \"No binding partner, PTM, or enzymatic role assigned to S8e specifically\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To test whether the ribosome architecture holds in natively purified particles and how it diverges from the host, cryo-EM reconstructions from blood-stage schizonts confirmed S8e as a small-subunit component and identified structural differences from mammalian ribosomes.\",\n      \"evidence\": \"Five sub-nanometer cryo-EM reconstructions with atomic model building by flexible fitting from P. falciparum schizont ribosomes\",\n      \"pmids\": [\n        \"26432834\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Establishes composition only; no experiment interrogates S8e function or interactions\",\n        \"Does not localize S8e-specific structural divergences from the host protein\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To determine whether S8e is part of the ribosome under physiological translation rather than only in purified particles, in situ cryo-ET of actively translating ribosomes inside infected erythrocytes confirmed S8e in the small subunit across elongation states.\",\n      \"evidence\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes yielding eight high-resolution structures of native translating ribosomes\",\n      \"pmids\": [\n        \"40825879\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No experiment isolates the contribution of S8e to elongation\",\n        \"No functional or interaction data specific to S8e\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether S8e has any function, interaction, or regulatory role beyond its structural membership in the 40S subunit, and whether it is dispensable or essential in P. falciparum.\",\n      \"evidence\": \"No functional, genetic, or biochemical experiment on S8e is present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout/knockdown data for S8e\",\n        \"No binding partners or PTMs identified\",\n        \"No S8e-specific role in translation initiation, elongation, or subunit assembly established\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0003735\",\n        \"supporting_discovery_ids\": [\n          0,\n          1,\n          2\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0006412\",\n        \"supporting_discovery_ids\": [\n          2\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"40S small ribosomal subunit of the P. falciparum 80S ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"S8e is known only as a structural component of the P. falciparum 40S ribosomal small subunit; no individual function, binding partner, PTM, or enzymatic activity has been experimentally attributed to it in the corpus.\",\n      \"Structural characterization spans purified 80S ribosomes (cryo-EM) and native translating ribosomes inside infected erythrocytes (in situ cryo-ET).\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1408600","name":null,"product":"40S ribosomal protein S8e, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1033900","name":null,"product":"40S ribosomal protein S8e, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1349800","name":null,"product":"40S ribosomal protein S8e, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}