{"gene":"PF3D7_1358800","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2014,"finding":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution revealed that RPS15 (40S ribosomal protein S15, PF3D7_1358800) is a component of the small (40S) ribosomal subunit; the structure showed emetine binding at the E-site of the small subunit, blocking 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 from a single study establishes RPS15 as a structural component of the 40S subunit, but no specific functional mutagenesis of RPS15 itself was performed","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Sub-nanometer cryo-EM reconstructions of P. falciparum 80S ribosomes from blood-stage schizonts, with atomic model building by flexible fitting, confirmed RPS15 as a structural constituent of the 40S small subunit and revealed structural/dynamic features differentiating the P. falciparum ribosome from mammalian ribosomes.","method":"Cryo-EM at sub-nanometer resolution with atomic model building by flexible fitting; five reconstructions from blood-stage schizonts","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — multiple cryo-EM reconstructions with atomic models from a single lab; RPS15 membership in the 40S subunit is confirmed structurally but no RPS15-specific functional experiments were performed","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Eight high-resolution in situ cryo-electron tomography structures of the native P. falciparum 80S ribosome in actively translating states inside infected erythrocytes confirmed RPS15 as part of the 40S subunit in the physiological cellular context; perturbation with a Plasmodium-specific translation inhibitor decreased elongation factor-bound ribosomal states and appeared to upregulate ribosome biogenesis.","method":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution structures of native ribosomes in actively translating states","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — highest-quality structural method (in situ cryo-ET) from a single study; RPS15 is confirmed as a 40S subunit component in native cellular context but no RPS15-specific functional dissection was reported","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1358800 (RPS15) is an established structural 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; beyond its membership in the small subunit, no specific enzymatic activity, binding partners unique to RPS15, or direct functional experiments on RPS15 itself have been reported in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_1358800 (RPS15) is a structural component of the small (40S) subunit of the Plasmodium falciparum 80S ribosome, established through high-resolution cryo-EM of the intact ribosome [PMID:24913268] and confirmed in native, actively translating ribosomes imaged in situ within infected erythrocytes by cryo-electron tomography [PMID:40825879]. Its assignment as a 40S constituent is consistent across multiple independent structural reconstructions from blood-stage parasites, which also delineate features distinguishing the P. falciparum ribosome from its mammalian counterpart [PMID:26432834]. Beyond this membership in the 40S small subunit, no enzymatic activity, RPS15-specific binding partners, or direct functional experiments on PF3D7_1358800 itself have been characterized in the available corpus; the emetine E-site block [PMID:24913268] and translation-inhibitor perturbations [PMID:40825879] reported in these studies concern the ribosome as a whole rather than RPS15 specifically.","teleology":[{"year":2014,"claim":"Establishing which proteins build the P. falciparum small ribosomal subunit was needed to define the parasite translation machinery; cryo-EM placed RPS15 as a structural constituent of the 40S subunit.","evidence":"Cryo-EM of the P. falciparum 80S ribosome with emetine at 3.2 Å resolution","pmids":["24913268"],"confidence":"Medium","gaps":["No RPS15-specific functional mutagenesis performed","Emetine binding maps to the small-subunit E-site, not to RPS15 itself","No RPS15-unique binding partners identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Whether RPS15 assignment held across independent reconstructions and how the parasite 40S differs from the mammalian one was addressed by multiple blood-stage schizont structures, confirming RPS15 membership and parasite-specific ribosomal features.","evidence":"Sub-nanometer cryo-EM with atomic model building by flexible fitting; five reconstructions from blood-stage schizonts","pmids":["26432834"],"confidence":"Medium","gaps":["RPS15-specific functional role not tested","Structural features attributed to the ribosome, not resolved to RPS15 function","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether RPS15 is part of the 40S subunit in the physiological cellular context of actively translating ribosomes was confirmed by in situ cryo-ET inside infected erythrocytes.","evidence":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution native translating-state structures","pmids":["40825879"],"confidence":"Medium","gaps":["No RPS15-specific functional dissection","Translation-inhibitor effects observed at the level of whole-ribosome states and biogenesis, not RPS15","No RPS15-specific interaction or activity resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_1358800 has any function or interaction distinct from its role as a 40S structural subunit remains unaddressed in the corpus.","evidence":"No direct functional experiment on RPS15 itself reported","pmids":[],"confidence":"Medium","gaps":["No RPS15-specific knockdown, knockout, or complementation","No RPS15-unique binding partners or extraribosomal activity characterized","No enzymatic activity assigned"],"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":["RPS15 membership in the 40S subunit is established purely by structural (cryo-EM and in situ cryo-ET) evidence; no RPS15-specific functional experiments exist in the corpus.","Emetine E-site binding and translation-inhibitor perturbations reported in these structures concern the whole ribosome, not RPS15 specifically."]}},"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":"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":4452,"output_tokens":1005,"usd":0.014216,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5753,"output_tokens":1788,"usd":0.036733,"stage2_stop_reason":"end_turn"},"total_usd":0.050949,"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 that RPS15 (40S ribosomal protein S15, PF3D7_1358800) is a component of the small (40S) ribosomal subunit; the structure showed emetine binding at the E-site of the small subunit, blocking 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 from a single study establishes RPS15 as a structural component of the 40S subunit, but no specific functional mutagenesis of RPS15 itself was performed\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Sub-nanometer cryo-EM reconstructions of P. falciparum 80S ribosomes from blood-stage schizonts, with atomic model building by flexible fitting, confirmed RPS15 as a structural constituent of the 40S small subunit and revealed structural/dynamic features differentiating the P. falciparum ribosome from mammalian ribosomes.\",\n      \"method\": \"Cryo-EM at sub-nanometer resolution with atomic model building by flexible fitting; five reconstructions from blood-stage schizonts\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — multiple cryo-EM reconstructions with atomic models from a single lab; RPS15 membership in the 40S subunit is confirmed structurally but no RPS15-specific functional experiments were performed\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Eight high-resolution in situ cryo-electron tomography structures of the native P. falciparum 80S ribosome in actively translating states inside infected erythrocytes confirmed RPS15 as part of the 40S subunit in the physiological cellular context; perturbation with a Plasmodium-specific translation inhibitor decreased elongation factor-bound ribosomal states and appeared to upregulate ribosome biogenesis.\",\n      \"method\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution structures of native ribosomes in actively translating states\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — highest-quality structural method (in situ cryo-ET) from a single study; RPS15 is confirmed as a 40S subunit component in native cellular context but no RPS15-specific functional dissection was reported\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1358800 (RPS15) is an established structural 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; beyond its membership in the small subunit, no specific enzymatic activity, binding partners unique to RPS15, or direct functional experiments on RPS15 itself have been reported in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1358800 (RPS15) is a structural component of the small (40S) subunit of the Plasmodium falciparum 80S ribosome, established through high-resolution cryo-EM of the intact ribosome [#0] and confirmed in native, actively translating ribosomes imaged in situ within infected erythrocytes by cryo-electron tomography [#2]. Its assignment as a 40S constituent is consistent across multiple independent structural reconstructions from blood-stage parasites, which also delineate features distinguishing the P. falciparum ribosome from its mammalian counterpart [#1]. Beyond this membership in the 40S small subunit, no enzymatic activity, RPS15-specific binding partners, or direct functional experiments on PF3D7_1358800 itself have been characterized in the available corpus; the emetine E-site block [#0] and translation-inhibitor perturbations [#2] reported in these studies concern the ribosome as a whole rather than RPS15 specifically.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing which proteins build the P. falciparum small ribosomal subunit was needed to define the parasite translation machinery; cryo-EM placed RPS15 as a structural constituent of the 40S subunit.\",\n      \"evidence\": \"Cryo-EM of the P. falciparum 80S ribosome with emetine at 3.2 Å resolution\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No RPS15-specific functional mutagenesis performed\",\n        \"Emetine binding maps to the small-subunit E-site, not to RPS15 itself\",\n        \"No RPS15-unique binding partners identified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether RPS15 assignment held across independent reconstructions and how the parasite 40S differs from the mammalian one was addressed by multiple blood-stage schizont structures, confirming RPS15 membership and parasite-specific ribosomal features.\",\n      \"evidence\": \"Sub-nanometer cryo-EM with atomic model building by flexible fitting; five reconstructions from blood-stage schizonts\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"RPS15-specific functional role not tested\",\n        \"Structural features attributed to the ribosome, not resolved to RPS15 function\",\n        \"Single lab\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether RPS15 is part of the 40S subunit in the physiological cellular context of actively translating ribosomes was confirmed by in situ cryo-ET inside infected erythrocytes.\",\n      \"evidence\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution native translating-state structures\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No RPS15-specific functional dissection\",\n        \"Translation-inhibitor effects observed at the level of whole-ribosome states and biogenesis, not RPS15\",\n        \"No RPS15-specific interaction or activity resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_1358800 has any function or interaction distinct from its role as a 40S structural subunit remains unaddressed in the corpus.\",\n      \"evidence\": \"No direct functional experiment on RPS15 itself reported\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No RPS15-specific knockdown, knockout, or complementation\",\n        \"No RPS15-unique binding partners or extraribosomal activity characterized\",\n        \"No enzymatic activity assigned\"\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\": [0, 2]}\n    ],\n    \"complexes\": [\n      \"40S small ribosomal subunit of the P. falciparum 80S ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"RPS15 membership in the 40S subunit is established purely by structural (cryo-EM and in situ cryo-ET) evidence; no RPS15-specific functional experiments exist in the corpus.\",\n      \"Emetine E-site binding and translation-inhibitor perturbations reported in these structures concern the whole ribosome, not RPS15 specifically.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1358800","name":null,"product":"40S ribosomal protein S15","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1135100","name":null,"product":"40S ribosomal protein S15, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1112500","name":null,"product":"40S ribosomal protein S15, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPS15","evaluation":null}