{"gene":"PF3D7_0316800","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2014,"finding":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution revealed the structural context of the small (40S) ribosomal subunit, of which S15A (PF3D7_0316800) is a component, bound to emetine at the E-site; the structure established that emetine blocks mRNA/tRNA translocation by binding the small subunit E-site.","method":"Cryo-EM structure determination at 3.2 Å resolution","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure of the intact ribosome establishes structural context; S15A is a component of the 40S subunit visualized, but no experiment specifically probes S15A's individual contribution or function beyond its membership in the complex.","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts at sub-nanometer resolution, with atomic models built by flexible fitting, revealed structural and dynamic features of the ribosome (including the 40S small subunit, of which S15A/PF3D7_0316800 is a component) that differentiate it from mammalian ribosomes.","method":"Cryo-EM with multiple reconstructions and flexible-fitting atomic model building from schizont-purified ribosomes","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — rigorous cryo-EM with atomic models; S15A is a structural component of the 40S subunit captured, but no functional experiment specifically interrogates S15A itself.","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In situ cryo-electron tomography of P. falciparum-infected erythrocytes determined eight high-resolution structures of the native malarial ribosome in actively translating states, establishing the structural environment of the 40S small subunit (of which S15A/PF3D7_0316800 is a constituent) within the native cellular context during translation elongation.","method":"In situ cryo-electron tomography in P. falciparum-infected erythrocytes; eight high-resolution structures of the native ribosome in translating states","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — highest-resolution in situ structural data for the native ribosome; S15A membership in the 40S subunit is captured but no experiment specifically probes S15A's individual role.","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0316800 (S15A) is a component of the P. falciparum 40S ribosomal small subunit, as established by multiple cryo-EM and in situ cryo-ET structures of the native Pf80S ribosome; beyond its structural membership in the small subunit, no experiment in the available literature has defined a specific mechanistic role for S15A itself."},"narrative":{"mechanistic_narrative":"PF3D7_0316800 (S15A) is a constituent protein of the small (40S) subunit of the Plasmodium falciparum 80S ribosome, established through successive structural studies of the native malarial ribosome [PMID:24913268, PMID:40825879]. It is resolved as a component of the 40S subunit in cryo-EM reconstructions of the intact 80S ribosome, including structures capturing emetine bound at the small-subunit E-site where it blocks mRNA/tRNA translocation [PMID:24913268], and in reconstructions from blood-stage schizonts that distinguish the parasite ribosome from its mammalian counterpart [PMID:26432834]. In situ cryo-electron tomography of infected erythrocytes further places the 40S subunit, and thus S15A, within the native cellular context of actively translating ribosomes during elongation [PMID:40825879]. Beyond its membership in the 40S small subunit, no experiment in the available corpus defines a specific mechanistic role, interaction, or individual function for S15A itself.","teleology":[{"year":2014,"claim":"Whether the P. falciparum 40S small subunit and its components could be resolved in structural detail was unknown; a high-resolution cryo-EM structure of the 80S ribosome placed S15A within the small subunit and revealed how the antimalarial emetine blocks translocation at the small-subunit E-site.","evidence":"Cryo-EM structure determination of the intact Pf80S ribosome at 3.2 Å resolution with bound emetine","pmids":["24913268"],"confidence":"Medium","gaps":["Does not probe S15A's individual contribution to subunit assembly or translation","No functional perturbation of S15A","No S15A-specific interactions defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"It was unclear how the parasite ribosome differs structurally and dynamically from the mammalian ribosome; sub-nanometer cryo-EM of schizont-purified ribosomes with flexible-fitted atomic models resolved distinguishing features of the small subunit that contains S15A.","evidence":"Cryo-EM reconstructions with flexible-fitting atomic model building from blood-stage schizont-purified ribosomes","pmids":["26432834"],"confidence":"Medium","gaps":["No S15A-specific functional role interrogated","Dynamics attributed to the subunit as a whole, not S15A individually"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether the malarial ribosome's translating states could be observed in the native cellular environment was unresolved; in situ cryo-electron tomography captured eight structures of actively translating ribosomes, situating the 40S subunit containing S15A within elongation in infected erythrocytes.","evidence":"In situ cryo-electron tomography in P. falciparum-infected erythrocytes yielding eight high-resolution structures of the native ribosome in translating states","pmids":["40825879"],"confidence":"Medium","gaps":["Does not isolate S15A's role in the native ribosome","No functional or knockdown data for S15A"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether S15A has any function beyond structural membership in the 40S subunit — its individual contribution to subunit assembly, translation fidelity, essentiality, or any regulatory role in P. falciparum has not been experimentally defined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genetic perturbation of S15A","No S15A-specific interaction or substrate data","No S15A-specific phenotype 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":["S15A is characterized in the available corpus only as a structural component of the 40S small subunit visualized in cryo-EM/cryo-ET structures of the native Pf80S ribosome; no experiment defines an individual function, interaction, or phenotype for S15A itself.","The 80S ribosome containing the S15A-bearing 40S subunit was resolved with emetine bound at the small-subunit E-site, where the drug blocks mRNA/tRNA translocation [#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":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":964,"usd":0.013912,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5669,"output_tokens":1808,"usd":0.036772,"stage2_stop_reason":"end_turn"},"total_usd":0.050684,"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 revealed the structural context of the small (40S) ribosomal subunit, of which S15A (PF3D7_0316800) is a component, bound to emetine at the E-site; the structure established that emetine blocks mRNA/tRNA translocation by binding the small subunit E-site.\",\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 of the intact ribosome establishes structural context; S15A is a component of the 40S subunit visualized, but no experiment specifically probes S15A's individual contribution or function beyond its membership in the complex.\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts at sub-nanometer resolution, with atomic models built by flexible fitting, revealed structural and dynamic features of the ribosome (including the 40S small subunit, of which S15A/PF3D7_0316800 is a component) that differentiate it from mammalian ribosomes.\",\n      \"method\": \"Cryo-EM with multiple reconstructions and flexible-fitting atomic model building from schizont-purified ribosomes\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — rigorous cryo-EM with atomic models; S15A is a structural component of the 40S subunit captured, but no functional experiment specifically interrogates S15A itself.\",\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 P. falciparum-infected erythrocytes determined eight high-resolution structures of the native malarial ribosome in actively translating states, establishing the structural environment of the 40S small subunit (of which S15A/PF3D7_0316800 is a constituent) within the native cellular context during translation elongation.\",\n      \"method\": \"In situ cryo-electron tomography in P. falciparum-infected erythrocytes; eight high-resolution structures of the native ribosome in translating states\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — highest-resolution in situ structural data for the native ribosome; S15A membership in the 40S subunit is captured but no experiment specifically probes S15A's individual role.\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0316800 (S15A) is a component of the P. falciparum 40S ribosomal small subunit, as established by multiple cryo-EM and in situ cryo-ET structures of the native Pf80S ribosome; beyond its structural membership in the small subunit, no experiment in the available literature has defined a specific mechanistic role for S15A itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0316800 (S15A) is a constituent protein of the small (40S) subunit of the Plasmodium falciparum 80S ribosome, established through successive structural studies of the native malarial ribosome [#0, #2]. It is resolved as a component of the 40S subunit in cryo-EM reconstructions of the intact 80S ribosome, including structures capturing emetine bound at the small-subunit E-site where it blocks mRNA/tRNA translocation [#0], and in reconstructions from blood-stage schizonts that distinguish the parasite ribosome from its mammalian counterpart [#1]. In situ cryo-electron tomography of infected erythrocytes further places the 40S subunit, and thus S15A, within the native cellular context of actively translating ribosomes during elongation [#2]. Beyond its membership in the 40S small subunit, no experiment in the available corpus defines a specific mechanistic role, interaction, or individual function for S15A itself.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether the P. falciparum 40S small subunit and its components could be resolved in structural detail was unknown; a high-resolution cryo-EM structure of the 80S ribosome placed S15A within the small subunit and revealed how the antimalarial emetine blocks translocation at the small-subunit E-site.\",\n      \"evidence\": \"Cryo-EM structure determination of the intact Pf80S ribosome at 3.2 Å resolution with bound emetine\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not probe S15A's individual contribution to subunit assembly or translation\", \"No functional perturbation of S15A\", \"No S15A-specific interactions defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"It was unclear how the parasite ribosome differs structurally and dynamically from the mammalian ribosome; sub-nanometer cryo-EM of schizont-purified ribosomes with flexible-fitted atomic models resolved distinguishing features of the small subunit that contains S15A.\",\n      \"evidence\": \"Cryo-EM reconstructions with flexible-fitting atomic model building from blood-stage schizont-purified ribosomes\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No S15A-specific functional role interrogated\", \"Dynamics attributed to the subunit as a whole, not S15A individually\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether the malarial ribosome's translating states could be observed in the native cellular environment was unresolved; in situ cryo-electron tomography captured eight structures of actively translating ribosomes, situating the 40S subunit containing S15A within elongation in infected erythrocytes.\",\n      \"evidence\": \"In situ cryo-electron tomography in P. falciparum-infected erythrocytes yielding eight high-resolution structures of the native ribosome in translating states\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not isolate S15A's role in the native ribosome\", \"No functional or knockdown data for S15A\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether S15A has any function beyond structural membership in the 40S subunit — its individual contribution to subunit assembly, translation fidelity, essentiality, or any regulatory role in P. falciparum has not been experimentally defined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No genetic perturbation of S15A\", \"No S15A-specific interaction or substrate data\", \"No S15A-specific phenotype established\"],\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      \"S15A is characterized in the available corpus only as a structural component of the 40S small subunit visualized in cryo-EM/cryo-ET structures of the native Pf80S ribosome; no experiment defines an individual function, interaction, or phenotype for S15A itself.\",\n      \"The 80S ribosome containing the S15A-bearing 40S subunit was resolved with emetine bound at the small-subunit E-site, where the drug blocks mRNA/tRNA translocation [#0].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0316800","name":null,"product":"40S ribosomal protein S15A, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0414600","name":null,"product":"40S ribosomal protein S15A, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0825000","name":null,"product":"40S ribosomal protein S15A, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}