{"gene":"PF3D7_0520000","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":2014,"finding":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution places RPS9 (PF3D7_0520000) as a component of the small (40S) ribosomal subunit. The structure reveals that emetine binds the E-site of the small subunit and 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 subunit composition including RPS9, but no functional experiments were directed specifically at RPS9; single study","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Cryo-EM reconstructions of the P. falciparum 80S ribosome purified from blood-stage schizonts confirm RPS9 (PF3D7_0520000) as a structural component of the 40S small subunit; atomic models were built by flexible fitting into sub-nanometer resolution density maps.","method":"Cryo-EM with flexible fitting and atomic model building from ribosomes purified from P. falciparum blood-stage schizonts","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM with atomic model building establishes RPS9 as a small subunit component, but no specific functional experiments targeted RPS9 itself; single lab","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In situ cryo-electron tomography of actively translating ribosomes inside P. falciparum-infected erythrocytes provides high-resolution structures of the native malarial ribosome in eight elongation states, establishing RPS9 (PF3D7_0520000) as part of the 40S small subunit in the physiological translation context; drug-induced perturbation with a Plasmodium-specific translation inhibitor reduced elongation factor-bound ribosomal states and apparently upregulated ribosome biogenesis.","method":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution structures of native translating ribosomes determined","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — highest-resolution in situ structural study establishing small subunit composition in native translation context, but no experiments specifically targeted RPS9; single study","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0520000 (RPS9) is a structural component of the 40S small ribosomal subunit of the P. falciparum 80S ribosome, as established by multiple cryo-EM and in situ cryo-electron tomography studies; no experiments have been directed specifically at its individual function or interactions beyond its membership in the small subunit."},"narrative":{"mechanistic_narrative":"PF3D7_0520000 (RPS9) is a structural component of the small (40S) subunit of the P. falciparum 80S ribosome, established by high-resolution cryo-EM of the purified ribosome [PMID:24913268, PMID:26432834] and by in situ cryo-electron tomography of actively translating ribosomes inside infected erythrocytes [PMID:40825879]. Its assignment to the 40S subunit holds both in ribosomes purified from blood-stage schizonts [PMID:26432834] and in the physiological translation context, where the native ribosome was resolved in eight elongation states [PMID:40825879]. No experiments in the available corpus have been directed specifically at the individual function, interactions, or essentiality of RPS9 beyond its membership in the small subunit; the surrounding structural work characterizes drug binding to the small subunit (emetine at the E-site blocking translocation [PMID:24913268]) and global translation dynamics rather than RPS9 itself.","teleology":[{"year":2014,"claim":"Whether RPS9 is a component of the P. falciparum ribosome and where it resides was resolved by placing it structurally within the 40S small subunit of the 80S ribosome.","evidence":"Cryo-EM of the P. falciparum 80S ribosome at 3.2 A in complex with emetine","pmids":["24913268"],"confidence":"Medium","gaps":["No functional experiment targeted RPS9 itself; assignment is compositional/structural only","No test of RPS9 essentiality or role in translation initiation/elongation","No interaction partners defined beyond co-membership in the small subunit"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Confirmation that RPS9's small-subunit assignment reflects the native blood-stage ribosome came from reconstructions of ribosomes purified from schizonts with atomic model building.","evidence":"Cryo-EM with flexible fitting and atomic model building from ribosomes purified from P. falciparum blood-stage schizonts","pmids":["26432834"],"confidence":"Medium","gaps":["Independent structural confirmation but still no RPS9-directed functional assay","Stage-specificity of RPS9 function not addressed","No reciprocal validation of RPS9 contacts within the subunit"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether the small-subunit composition including RPS9 is preserved during active translation in the physiological cellular environment was addressed by resolving native translating ribosomes in situ across eight elongation states.","evidence":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution structures of native translating ribosomes","pmids":["40825879"],"confidence":"Medium","gaps":["RPS9 was observed as part of the subunit but no perturbation of RPS9 was performed","Contribution of RPS9 to elongation-state transitions unknown","Drug-induced changes were interpreted at the level of the ribosome, not RPS9 specifically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The individual function of RPS9 — its specific role in translation, its assembly requirements, its essentiality, and any non-ribosomal or moonlighting activity in P. falciparum — remains uncharacterized.","evidence":"No RPS9-directed functional or genetic experiment exists in the available corpus","pmids":[],"confidence":"Medium","gaps":["No knockdown, knockout, or complementation data for RPS9","No RPS9-specific interaction or crosslinking data beyond structural co-membership","No evidence on RPS9 as an antimalarial target distinct from the ribosome as a whole"],"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":["Assignment of RPS9 to the 40S subunit is compositional/structural (cryo-EM and cryo-ET); no experiment has targeted RPS9's individual function.","Emetine binding at the small-subunit E-site blocking mRNA/tRNA translocation is a property of the small subunit context, not demonstrated for RPS9 specifically [#0]."]}},"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":"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":"19929377","id":"PMC_19929377","title":"Susceptibility of Plasmodium falciparum isolates to doxycycline is associated with pftetQ sequence polymorphisms and pftetQ and pfmdt copy numbers.","date":"2010","source":"The Journal of infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/19929377","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfRPS9"],"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":5003,"output_tokens":950,"usd":0.01463,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5665,"output_tokens":1827,"usd":0.037,"stage2_stop_reason":"end_turn"},"total_usd":0.05163,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","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 places RPS9 (PF3D7_0520000) as a component of the small (40S) ribosomal subunit. The structure reveals that emetine binds the E-site of the small subunit and 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 subunit composition including RPS9, but no functional experiments were directed specifically at RPS9; 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 the P. falciparum 80S ribosome purified from blood-stage schizonts confirm RPS9 (PF3D7_0520000) as a structural component of the 40S small subunit; atomic models were built by flexible fitting into sub-nanometer resolution density maps.\",\n      \"method\": \"Cryo-EM with flexible fitting and atomic model building from ribosomes purified from P. falciparum blood-stage schizonts\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM with atomic model building establishes RPS9 as a small subunit component, but no specific functional experiments targeted RPS9 itself; single lab\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In situ cryo-electron tomography of actively translating ribosomes inside P. falciparum-infected erythrocytes provides high-resolution structures of the native malarial ribosome in eight elongation states, establishing RPS9 (PF3D7_0520000) as part of the 40S small subunit in the physiological translation context; drug-induced perturbation with a Plasmodium-specific translation inhibitor reduced elongation factor-bound ribosomal states and apparently upregulated ribosome biogenesis.\",\n      \"method\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution structures of native translating ribosomes determined\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — highest-resolution in situ structural study establishing small subunit composition in native translation context, but no experiments specifically targeted RPS9; single study\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0520000 (RPS9) is a structural component of the 40S small ribosomal subunit of the P. falciparum 80S ribosome, as established by multiple cryo-EM and in situ cryo-electron tomography studies; no experiments have been directed specifically at its individual function or interactions beyond its membership in the small subunit.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0520000 (RPS9) is a structural component of the small (40S) subunit of the P. falciparum 80S ribosome, established by high-resolution cryo-EM of the purified ribosome [#0, #1] and by in situ cryo-electron tomography of actively translating ribosomes inside infected erythrocytes [#2]. Its assignment to the 40S subunit holds both in ribosomes purified from blood-stage schizonts [#1] and in the physiological translation context, where the native ribosome was resolved in eight elongation states [#2]. No experiments in the available corpus have been directed specifically at the individual function, interactions, or essentiality of RPS9 beyond its membership in the small subunit; the surrounding structural work characterizes drug binding to the small subunit (emetine at the E-site blocking translocation [#0]) and global translation dynamics rather than RPS9 itself.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether RPS9 is a component of the P. falciparum ribosome and where it resides was resolved by placing it structurally within the 40S small subunit of the 80S ribosome.\",\n      \"evidence\": \"Cryo-EM of the P. falciparum 80S ribosome at 3.2 A in complex with emetine\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional experiment targeted RPS9 itself; assignment is compositional/structural only\",\n        \"No test of RPS9 essentiality or role in translation initiation/elongation\",\n        \"No interaction partners defined beyond co-membership in the small subunit\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Confirmation that RPS9's small-subunit assignment reflects the native blood-stage ribosome came from reconstructions of ribosomes purified from schizonts with atomic model building.\",\n      \"evidence\": \"Cryo-EM with flexible fitting and atomic model building from ribosomes purified from P. falciparum blood-stage schizonts\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Independent structural confirmation but still no RPS9-directed functional assay\",\n        \"Stage-specificity of RPS9 function not addressed\",\n        \"No reciprocal validation of RPS9 contacts within the subunit\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether the small-subunit composition including RPS9 is preserved during active translation in the physiological cellular environment was addressed by resolving native translating ribosomes in situ across eight elongation states.\",\n      \"evidence\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution structures of native translating ribosomes\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"RPS9 was observed as part of the subunit but no perturbation of RPS9 was performed\",\n        \"Contribution of RPS9 to elongation-state transitions unknown\",\n        \"Drug-induced changes were interpreted at the level of the ribosome, not RPS9 specifically\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The individual function of RPS9 — its specific role in translation, its assembly requirements, its essentiality, and any non-ribosomal or moonlighting activity in P. falciparum — remains uncharacterized.\",\n      \"evidence\": \"No RPS9-directed functional or genetic experiment exists in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No knockdown, knockout, or complementation data for RPS9\",\n        \"No RPS9-specific interaction or crosslinking data beyond structural co-membership\",\n        \"No evidence on RPS9 as an antimalarial target distinct from the ribosome as a whole\"\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]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0022627\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"40S small ribosomal subunit of the P. falciparum 80S ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Assignment of RPS9 to the 40S subunit is compositional/structural (cryo-EM and cryo-ET); no experiment has targeted RPS9's individual function.\",\n      \"Emetine binding at the small-subunit E-site blocking mRNA/tRNA translocation is a property of the small subunit context, not demonstrated for RPS9 specifically [#0].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0520000","name":null,"product":"40S ribosomal protein S9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1234800","name":null,"product":"40S ribosomal protein S9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1013100","name":null,"product":"40S ribosomal protein S9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPS9","evaluation":null}