{"gene":"PF3D7_1461300","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 was determined, revealing the architecture of the small (40S) subunit, within which S28e (PF3D7_1461300) resides as a component of the ribosomal small subunit. The structure established that emetine binds the E-site of the small subunit to block mRNA/tRNA translocation, placing the 40S subunit proteins including S28e in the context of drug interaction at the ribosome.","method":"Cryo-EM structure determination at 3.2 Å resolution of the P. falciparum 80S ribosome in complex with emetine","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure of the intact ribosome is Tier 1, but the abstract establishes nothing specific about PF3D7_1461300 beyond its membership in the 40S subunit complex; no finding is uniquely attributed to S28e itself","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Multiple cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts at sub-nanometer resolution established structural and dynamic features of the ribosome (including the 40S small subunit, of which S28e/PF3D7_1461300 is a component) that differentiate it from mammalian ribosomes; atomic models were built by flexible fitting into the density maps.","method":"Cryo-EM with atomic model building by flexible fitting from P. falciparum blood-stage schizont ribosomes","journal":"Nucleic acids research","confidence":"Low","confidence_rationale":"Tier 1 / Weak — rigorous cryo-EM with atomic modeling, but the abstract attributes no specific finding to S28e/PF3D7_1461300 individually; membership in the 40S subunit is the only inference","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In situ cryo-electron tomography of P. falciparum-infected erythrocytes yielded eight high-resolution structures of the native malarial ribosome in actively translating states, providing molecular-resolution views of the 40S small subunit (which contains S28e/PF3D7_1461300) within the native cellular context; following treatment with a Plasmodium-specific translation inhibitor, elongation factor-bound ribosomal states decreased and apparent ribosome biogenesis was upregulated.","method":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; drug perturbation experiments","journal":"Nature structural & molecular biology","confidence":"Low","confidence_rationale":"Tier 1 / Weak — highly rigorous in situ structural approach, but no finding is specifically attributed to S28e/PF3D7_1461300; only its membership in the 40S ribosomal small subunit can be inferred","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1461300 (S28e) is a component of the P. falciparum 40S ribosomal small subunit, as established by multiple cryo-EM structures of the intact Pf80S ribosome; no experimental findings specific to the molecular function, interactions, or modification of S28e itself have been reported in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_1461300 (S28e) is annotated as a component of the small (40S) subunit of the P. falciparum 80S ribosome, established solely through cryo-EM and cryo-electron tomography of the intact ribosome in which S28e is placed as one of the 40S subunit proteins [PMID:24913268, PMID:26432834, PMID:40825879]. These structures resolved the 40S subunit in the context of drug interaction — emetine binding the E-site to block mRNA/tRNA translocation [PMID:24913268] — and in native, actively translating states within infected erythrocytes [PMID:40825879], but no finding in the available corpus is uniquely attributed to S28e itself. Beyond its membership in the 40S small subunit complex, no molecular function, interaction, substrate, localization, or modification specific to PF3D7_1461300 has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"The first high-resolution structure of the P. falciparum 80S ribosome placed the 40S small subunit proteins, including S28e, within the assembled ribosome and in the context of antimalarial drug binding, establishing the structural setting in which S28e resides.","evidence":"Cryo-EM at 3.2 Å of the P. falciparum 80S ribosome bound to emetine","pmids":["24913268"],"confidence":"Low","gaps":["No finding uniquely attributed to S28e beyond membership in the 40S subunit","No S28e-specific interactions, function, or modification defined","Emetine binds the E-site, not S28e directly"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Sub-nanometer cryo-EM reconstructions from blood-stage schizonts refined the atomic model of the malarial 40S subunit and highlighted features distinguishing it from mammalian ribosomes, extending the structural context of S28e as a 40S component.","evidence":"Cryo-EM with flexible-fitting atomic model building from P. falciparum schizont ribosomes","pmids":["26432834"],"confidence":"Low","gaps":["No specific structural or functional role assigned to S28e","Divergence from mammalian ribosome not localized to S28e"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"In situ cryo-electron tomography captured the native malarial ribosome in actively translating states inside infected erythrocytes and monitored responses to a Plasmodium-specific translation inhibitor, situating the 40S subunit (and thus S28e) in its cellular translational context.","evidence":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes with drug perturbation","pmids":["40825879"],"confidence":"Low","gaps":["No finding specific to S28e distinct from the whole 40S subunit","Drug effect described for ribosome states generally, not S28e","No S28e-level dynamics resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether S28e has any function, interaction, or property distinct from its structural membership in the 40S subunit remains entirely uncharacterized in the available corpus.","evidence":"No S28e-specific experimental study present in the timeline","pmids":[],"confidence":"Low","gaps":["No S28e-specific molecular function established","No interactors or modifications of S28e reported","No genetic or biochemical perturbation of S28e alone"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["40S small ribosomal subunit (P. falciparum)","Pf80S ribosome"],"partners":[],"other_free_text":["S28e is placed as a 40S small subunit component only through whole-ribosome cryo-EM/cryo-ET; no finding in the corpus is uniquely attributed to PF3D7_1461300 itself.","Emetine binds the E-site of the small subunit to block mRNA/tRNA translocation [#0]; this is a ribosome-level, not S28e-specific, interaction."]}},"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":"20078859","id":"PMC_20078859","title":"Assessing functional annotation transfers with inter-species conserved coexpression: application to Plasmodium falciparum.","date":"2010","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/20078859","citation_count":12,"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":4968,"output_tokens":1050,"usd":0.015327,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5777,"output_tokens":1762,"usd":0.036467,"stage2_stop_reason":"end_turn"},"total_usd":0.051794,"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 was determined, revealing the architecture of the small (40S) subunit, within which S28e (PF3D7_1461300) resides as a component of the ribosomal small subunit. The structure established that emetine binds the E-site of the small subunit to block mRNA/tRNA translocation, placing the 40S subunit proteins including S28e in the context of drug interaction at the ribosome.\",\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\": \"Low\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM structure of the intact ribosome is Tier 1, but the abstract establishes nothing specific about PF3D7_1461300 beyond its membership in the 40S subunit complex; no finding is uniquely attributed to S28e itself\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Multiple cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts at sub-nanometer resolution established structural and dynamic features of the ribosome (including the 40S small subunit, of which S28e/PF3D7_1461300 is a component) that differentiate it from mammalian ribosomes; atomic models were built by flexible fitting into the density maps.\",\n      \"method\": \"Cryo-EM with 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 — rigorous cryo-EM with atomic modeling, but the abstract attributes no specific finding to S28e/PF3D7_1461300 individually; membership in the 40S subunit is the only inference\",\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 yielded eight high-resolution structures of the native malarial ribosome in actively translating states, providing molecular-resolution views of the 40S small subunit (which contains S28e/PF3D7_1461300) within the native cellular context; following treatment with a Plasmodium-specific translation inhibitor, elongation factor-bound ribosomal states decreased and apparent ribosome biogenesis was upregulated.\",\n      \"method\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; drug perturbation experiments\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 1 / Weak — highly rigorous in situ structural approach, but no finding is specifically attributed to S28e/PF3D7_1461300; only its membership in the 40S ribosomal small subunit can be inferred\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1461300 (S28e) is a component of the P. falciparum 40S ribosomal small subunit, as established by multiple cryo-EM structures of the intact Pf80S ribosome; no experimental findings specific to the molecular function, interactions, or modification of S28e itself have been reported in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1461300 (S28e) is annotated as a component of the small (40S) subunit of the P. falciparum 80S ribosome, established solely through cryo-EM and cryo-electron tomography of the intact ribosome in which S28e is placed as one of the 40S subunit proteins [#0, #1, #2]. These structures resolved the 40S subunit in the context of drug interaction — emetine binding the E-site to block mRNA/tRNA translocation [#0] — and in native, actively translating states within infected erythrocytes [#2], but no finding in the available corpus is uniquely attributed to S28e itself. Beyond its membership in the 40S small subunit complex, no molecular function, interaction, substrate, localization, or modification specific to PF3D7_1461300 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"The first high-resolution structure of the P. falciparum 80S ribosome placed the 40S small subunit proteins, including S28e, within the assembled ribosome and in the context of antimalarial drug binding, establishing the structural setting in which S28e resides.\",\n      \"evidence\": \"Cryo-EM at 3.2 Å of the P. falciparum 80S ribosome bound to emetine\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No finding uniquely attributed to S28e beyond membership in the 40S subunit\",\n        \"No S28e-specific interactions, function, or modification defined\",\n        \"Emetine binds the E-site, not S28e directly\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Sub-nanometer cryo-EM reconstructions from blood-stage schizonts refined the atomic model of the malarial 40S subunit and highlighted features distinguishing it from mammalian ribosomes, extending the structural context of S28e as a 40S component.\",\n      \"evidence\": \"Cryo-EM with flexible-fitting atomic model building from P. falciparum schizont ribosomes\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No specific structural or functional role assigned to S28e\",\n        \"Divergence from mammalian ribosome not localized to S28e\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"In situ cryo-electron tomography captured the native malarial ribosome in actively translating states inside infected erythrocytes and monitored responses to a Plasmodium-specific translation inhibitor, situating the 40S subunit (and thus S28e) in its cellular translational context.\",\n      \"evidence\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes with drug perturbation\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No finding specific to S28e distinct from the whole 40S subunit\",\n        \"Drug effect described for ribosome states generally, not S28e\",\n        \"No S28e-level dynamics resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether S28e has any function, interaction, or property distinct from its structural membership in the 40S subunit remains entirely uncharacterized in the available corpus.\",\n      \"evidence\": \"No S28e-specific experimental study present in the timeline\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No S28e-specific molecular function established\",\n        \"No interactors or modifications of S28e reported\",\n        \"No genetic or biochemical perturbation of S28e alone\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\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 (P. falciparum)\",\n      \"Pf80S ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"S28e is placed as a 40S small subunit component only through whole-ribosome cryo-EM/cryo-ET; no finding in the corpus is uniquely attributed to PF3D7_1461300 itself.\",\n      \"Emetine binds the E-site of the small subunit to block mRNA/tRNA translocation [#0]; this is a ribosome-level, not S28e-specific, interaction.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1461300","name":null,"product":"40S ribosomal protein S28e, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1325000","name":null,"product":"40S ribosomal protein S28e, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1220400","name":null,"product":"40S ribosomal protein S28e, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}