{"gene":"PF3D7_0813900","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2014,"finding":"PF3D7_0813900 (RPS16), as part of the P. falciparum 40S ribosomal small subunit, was visualized at 3.2 Å resolution in a cryo-EM structure of the P. falciparum 80S ribosome bound to emetine. The small subunit E-site, where emetine binds and blocks mRNA/tRNA translocation, is structurally defined, placing RPS16 in the context of the assembled small subunit.","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 of the whole ribosome establishes small-subunit context, but no experiment specifically interrogates RPS16 function or its individual contribution; single study","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"PF3D7_0813900 (RPS16), as a component of the P. falciparum 40S small subunit, was resolved in five cryo-EM reconstructions of the P. falciparum 80S ribosome purified from blood-stage schizonts at sub-nanometer resolution, revealing structural and dynamic features that differentiate the P. falciparum ribosome from mammalian ribosomes during active translation.","method":"Cryo-EM reconstruction (five structures) with atomic model building by flexible fitting, from ribosomes purified from P. falciparum blood-stage schizonts","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — multiple cryo-EM reconstructions with atomic modeling, but no experiment individually interrogates RPS16; single lab","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"PF3D7_0813900 (RPS16), as part of the P. falciparum 40S small subunit, was visualized in eight high-resolution structures of the native malarial ribosome in actively translating states inside P. falciparum-infected human erythrocytes using in situ cryo-electron tomography, establishing the small subunit's structural context during elongation and following perturbation by a Plasmodium-specific translation inhibitor.","method":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution native ribosome structures determined","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — rigorous in situ structural approach, but no experiment specifically dissects RPS16's individual contribution; single study","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"The genomic locus encoding RPS16 (PF3D7_0813900) in P. falciparum participates in a highly conserved synteny with fibrillarin across multiple eukaryotes, suggesting a conserved genomic linkage, though no functional experiment was performed specifically on the P. falciparum gene.","method":"Comparative genomic synteny mapping of operon gene orthologues across eukaryotes","journal":"Folia biologica","confidence":"Low","confidence_rationale":"Tier 4 / Weak — purely computational/comparative genomic analysis with no functional experiment on RPS16 itself","pmids":["15055736"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0813900 (RPS16) is a component of the P. falciparum 40S ribosomal small subunit, structurally characterized as part of the assembled 80S ribosome by cryo-EM (including in situ during active translation); no experiments have individually interrogated its specific function, binding partners, or post-translational modifications beyond its membership in the ribosomal small subunit complex."},"narrative":{"mechanistic_narrative":"PF3D7_0813900 (RPS16) is a component of the 40S small ribosomal subunit of Plasmodium falciparum, resolved within the assembled 80S ribosome by high-resolution cryo-EM of purified particles and, more recently, by in situ cryo-electron tomography of actively translating ribosomes inside infected human erythrocytes [PMID:24913268, PMID:26432834, PMID:40825879]. In these structures RPS16 is placed in the small-subunit context alongside the E-site region where the translation inhibitor emetine binds to block mRNA/tRNA translocation, and it is captured during elongation states that distinguish the parasite ribosome from the mammalian ribosome [PMID:24913268, PMID:40825879]. Beyond its membership in the 40S small subunit as defined by these whole-ribosome structures, no experiment in the available corpus has individually interrogated the specific function, binding partners, or post-translational modifications of PF3D7_0813900.","teleology":[{"year":2004,"claim":"Before any functional work, comparative genomics asked whether the RPS16 locus showed evolutionary constraints hinting at conserved regulation, establishing a conserved genomic linkage with fibrillarin across eukaryotes.","evidence":"Comparative genomic synteny mapping of operon gene orthologues across eukaryotes","pmids":["15055736"],"confidence":"Low","gaps":["Purely computational; no functional experiment performed on the P. falciparum gene","Synteny with fibrillarin does not establish any functional relationship for RPS16","No evidence linking the genomic linkage to ribosome function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"The unknown was where RPS16 sits within the parasite ribosome; a cryo-EM structure of the 80S ribosome placed RPS16 in the assembled 40S small subunit and defined the small-subunit E-site targeted by emetine.","evidence":"Cryo-EM structure determination at 3.2 Å of the P. falciparum 80S ribosome bound to emetine","pmids":["24913268"],"confidence":"Medium","gaps":["No experiment dissects RPS16's individual contribution to translation","No binding partners specific to RPS16 identified","Function beyond structural membership in the small subunit unaddressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To determine whether the parasite ribosome differs from the mammalian ribosome during translation, multiple cryo-EM reconstructions from blood-stage schizonts resolved RPS16 within the 40S subunit and revealed parasite-specific structural and dynamic features.","evidence":"Five cryo-EM reconstructions with flexible-fitting atomic modeling from schizont-purified ribosomes","pmids":["26432834"],"confidence":"Medium","gaps":["RPS16 not individually interrogated","Parasite-specific features not attributed to RPS16 in particular","No functional consequence of the observed dynamics tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"The remaining question was how the small subunit behaves during native translation in vivo; in situ cryo-electron tomography captured RPS16 within actively translating ribosomes inside infected erythrocytes and after inhibitor perturbation.","evidence":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight native ribosome structures","pmids":["40825879"],"confidence":"Medium","gaps":["No experiment isolates RPS16's role in the elongation states observed","Post-translational modifications of RPS16 not addressed","No genetic or biochemical test of RPS16 essentiality or partners"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_0813900 has any function, interaction, or regulatory role beyond structural membership in the 40S small subunit remains uncharacterized.","evidence":"No functional, genetic, or biochemical study of RPS16 itself in the available corpus","pmids":[],"confidence":"Low","gaps":["No knockdown/knockout phenotype for RPS16","No RPS16-specific binding partners or PTMs identified","No experiment separates RPS16's contribution from the rest of the small subunit"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["40S small ribosomal subunit (P. falciparum)","80S ribosome (P. falciparum)"],"partners":[],"other_free_text":["Visualized within the assembled 80S ribosome near the small-subunit E-site where emetine binds [#0]","Resolved in actively translating native ribosomes in situ inside infected erythrocytes [#2]","Genomic locus shows conserved synteny with fibrillarin across eukaryotes (computational only) [#3]","No experiment individually interrogates RPS16 function, partners, or PTMs; role limited to small-subunit membership"]}},"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":"16879650","id":"PMC_16879650","title":"Malaria transmission-blocking antigen, Pfs230, mediates human red blood cell binding to exflagellating male parasites and oocyst production.","date":"2006","source":"Molecular 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gametocytes.","date":"2007","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/17367781","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28416533","id":"PMC_28416533","title":"Capturing in vivo RNA transcriptional dynamics from the malaria parasite Plasmodium falciparum.","date":"2017","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/28416533","citation_count":40,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12067340","id":"PMC_12067340","title":"Targeting and sequestration of truncated Pfs230 in an intraerythrocytic compartment during Plasmodium falciparum gametocytogenesis.","date":"2002","source":"Molecular 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biologica","url":"https://pubmed.ncbi.nlm.nih.gov/15055736","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["S16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12507,"output_tokens":1219,"usd":0.027903,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6034,"output_tokens":2093,"usd":0.041247,"stage2_stop_reason":"end_turn"},"total_usd":0.06915,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"PF3D7_0813900 (RPS16), as part of the P. falciparum 40S ribosomal small subunit, was visualized at 3.2 Å resolution in a cryo-EM structure of the P. falciparum 80S ribosome bound to emetine. The small subunit E-site, where emetine binds and blocks mRNA/tRNA translocation, is structurally defined, placing RPS16 in the context of the assembled small subunit.\",\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 of the whole ribosome establishes small-subunit context, but no experiment specifically interrogates RPS16 function or its individual contribution; single study\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"PF3D7_0813900 (RPS16), as a component of the P. falciparum 40S small subunit, was resolved in five cryo-EM reconstructions of the P. falciparum 80S ribosome purified from blood-stage schizonts at sub-nanometer resolution, revealing structural and dynamic features that differentiate the P. falciparum ribosome from mammalian ribosomes during active translation.\",\n      \"method\": \"Cryo-EM reconstruction (five structures) with atomic model building by flexible fitting, from ribosomes purified from P. falciparum blood-stage schizonts\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — multiple cryo-EM reconstructions with atomic modeling, but no experiment individually interrogates RPS16; single lab\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PF3D7_0813900 (RPS16), as part of the P. falciparum 40S small subunit, was visualized in eight high-resolution structures of the native malarial ribosome in actively translating states inside P. falciparum-infected human erythrocytes using in situ cryo-electron tomography, establishing the small subunit's structural context during elongation and following perturbation by a Plasmodium-specific translation inhibitor.\",\n      \"method\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight high-resolution native ribosome structures determined\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — rigorous in situ structural approach, but no experiment specifically dissects RPS16's individual contribution; single study\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The genomic locus encoding RPS16 (PF3D7_0813900) in P. falciparum participates in a highly conserved synteny with fibrillarin across multiple eukaryotes, suggesting a conserved genomic linkage, though no functional experiment was performed specifically on the P. falciparum gene.\",\n      \"method\": \"Comparative genomic synteny mapping of operon gene orthologues across eukaryotes\",\n      \"journal\": \"Folia biologica\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — purely computational/comparative genomic analysis with no functional experiment on RPS16 itself\",\n      \"pmids\": [\"15055736\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0813900 (RPS16) is a component of the P. falciparum 40S ribosomal small subunit, structurally characterized as part of the assembled 80S ribosome by cryo-EM (including in situ during active translation); no experiments have individually interrogated its specific function, binding partners, or post-translational modifications beyond its membership in the ribosomal small subunit complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0813900 (RPS16) is a component of the 40S small ribosomal subunit of Plasmodium falciparum, resolved within the assembled 80S ribosome by high-resolution cryo-EM of purified particles and, more recently, by in situ cryo-electron tomography of actively translating ribosomes inside infected human erythrocytes [#0, #1, #2]. In these structures RPS16 is placed in the small-subunit context alongside the E-site region where the translation inhibitor emetine binds to block mRNA/tRNA translocation, and it is captured during elongation states that distinguish the parasite ribosome from the mammalian ribosome [#0, #2]. Beyond its membership in the 40S small subunit as defined by these whole-ribosome structures, no experiment in the available corpus has individually interrogated the specific function, binding partners, or post-translational modifications of PF3D7_0813900.\"\n,\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Before any functional work, comparative genomics asked whether the RPS16 locus showed evolutionary constraints hinting at conserved regulation, establishing a conserved genomic linkage with fibrillarin across eukaryotes.\",\n      \"evidence\": \"Comparative genomic synteny mapping of operon gene orthologues across eukaryotes\",\n      \"pmids\": [\"15055736\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational; no functional experiment performed on the P. falciparum gene\",\n        \"Synteny with fibrillarin does not establish any functional relationship for RPS16\",\n        \"No evidence linking the genomic linkage to ribosome function\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"The unknown was where RPS16 sits within the parasite ribosome; a cryo-EM structure of the 80S ribosome placed RPS16 in the assembled 40S small subunit and defined the small-subunit E-site targeted by emetine.\",\n      \"evidence\": \"Cryo-EM structure determination at 3.2 Å of the P. falciparum 80S ribosome bound to emetine\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No experiment dissects RPS16's individual contribution to translation\",\n        \"No binding partners specific to RPS16 identified\",\n        \"Function beyond structural membership in the small subunit unaddressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To determine whether the parasite ribosome differs from the mammalian ribosome during translation, multiple cryo-EM reconstructions from blood-stage schizonts resolved RPS16 within the 40S subunit and revealed parasite-specific structural and dynamic features.\",\n      \"evidence\": \"Five cryo-EM reconstructions with flexible-fitting atomic modeling from schizont-purified ribosomes\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"RPS16 not individually interrogated\",\n        \"Parasite-specific features not attributed to RPS16 in particular\",\n        \"No functional consequence of the observed dynamics tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The remaining question was how the small subunit behaves during native translation in vivo; in situ cryo-electron tomography captured RPS16 within actively translating ribosomes inside infected erythrocytes and after inhibitor perturbation.\",\n      \"evidence\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; eight native ribosome structures\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No experiment isolates RPS16's role in the elongation states observed\",\n        \"Post-translational modifications of RPS16 not addressed\",\n        \"No genetic or biochemical test of RPS16 essentiality or partners\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0813900 has any function, interaction, or regulatory role beyond structural membership in the 40S small subunit remains uncharacterized.\",\n      \"evidence\": \"No functional, genetic, or biochemical study of RPS16 itself in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No knockdown/knockout phenotype for RPS16\",\n        \"No RPS16-specific binding partners or PTMs identified\",\n        \"No experiment separates RPS16's contribution from the rest of the small subunit\"\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    \"pathway\": [\n      {\"term_id\": \"GO:0006414\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\n      \"40S small ribosomal subunit (P. falciparum)\",\n      \"80S ribosome (P. falciparum)\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Visualized within the assembled 80S ribosome near the small-subunit E-site where emetine binds [#0]\",\n      \"Resolved in actively translating native ribosomes in situ inside infected erythrocytes [#2]\",\n      \"Genomic locus shows conserved synteny with fibrillarin across eukaryotes (computational only) [#3]\",\n      \"No experiment individually interrogates RPS16 function, partners, or PTMs; role limited to small-subunit membership\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0813900","name":null,"product":"40S ribosomal protein S16, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1423600","name":null,"product":"40S ribosomal protein S16, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1426400","name":null,"product":"40S ribosomal protein S16, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPS16","evaluation":null}