{"gene":"PF3D7_1144000","run_date":"2026-09-08T14:19:05","timeline":{"discoveries":[{"year":2014,"finding":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution revealed that RPS21 (PF3D7_1144000) is a component of the small (40S) subunit; the structure showed emetine binds the E-site of the small subunit, blocking mRNA/tRNA translocation, establishing the structural context of the 40S ribosomal protein complement including RPS21.","method":"Cryo-EM structure determination at 3.2 Å resolution of P. falciparum 80S ribosome in complex with emetine","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure establishes RPS21 as a structural component of the 40S subunit, but no functional experiment specific to RPS21 itself was performed; finding about RPS21 is incidental to the global ribosome structure","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Five cryo-EM reconstructions of P. falciparum blood-stage schizont ribosomes at sub-nanometer resolution and atomic model building confirmed RPS21 (PF3D7_1144000) as part of the 40S small subunit and revealed structural and dynamic features of the P. falciparum ribosome distinguishing it from mammalian ribosomes.","method":"Cryo-EM reconstructions of native ribosomes purified from P. falciparum schizonts; flexible fitting of atomic models into density maps","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — multiple cryo-EM reconstructions with atomic model building confirm RPS21 as a structural component of the small subunit, but no functional experiment specific to RPS21 was performed","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, providing molecular-resolution visualization of the 40S subunit (which contains RPS21/PF3D7_1144000) within the native cellular context; translation inhibitor treatment decreased elongation factor-bound ribosomal states and triggered apparent upregulation of ribosome biogenesis.","method":"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; high-resolution structural determination of native ribosomes in translating states with and without a Plasmodium-specific translation inhibitor","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in situ cryo-ET provides high-resolution structural context for RPS21 as part of the native 40S subunit, but no experiment specifically interrogates RPS21 function; finding is incidental to the global ribosome study","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1144000 (RPS21) is established as a structural component of the P. falciparum 40S ribosomal small subunit, as demonstrated by cryo-EM and in situ cryo-ET structures of the native 80S ribosome; beyond its membership in the small subunit, no experiment has established a specific functional, catalytic, or regulatory role for RPS21 itself."},"narrative":{"mechanistic_narrative":"PF3D7_1144000 (RPS21) is a structural component of the small (40S) subunit of the P. falciparum 80S ribosome, established by cryo-EM structures of the native ribosome that resolved the 40S ribosomal protein complement, including RPS21, and distinguished the parasite ribosome from its mammalian counterpart [PMID:24913268, PMID:26432834]. In situ cryo-electron tomography of P. falciparum-infected erythrocytes has since visualized the 40S subunit containing RPS21 within actively translating native ribosomes in the cellular context [PMID:40825879]. Beyond its membership in the 40S small subunit, no experiment in the available corpus has established a specific catalytic, regulatory, or functional role for RPS21 itself.","teleology":[{"year":2014,"claim":"Whether RPS21 is part of the parasite ribosome and how the P. falciparum small subunit is organized was unresolved; a high-resolution structure was needed to place RPS21 within the assembled ribosome.","evidence":"Cryo-EM structure at 3.2 Å of the P. falciparum 80S ribosome bound to emetine, resolving the 40S protein complement","pmids":["24913268"],"confidence":"Medium","gaps":["No functional experiment specific to RPS21 was performed; its role is inferred only from complex membership","Does not establish whether RPS21 has any activity distinct from structural scaffolding"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Whether the placement of RPS21 in the 40S subunit was robust and how the parasite ribosome differs structurally from the mammalian ribosome required independent reconstructions.","evidence":"Multiple cryo-EM reconstructions of native schizont-stage ribosomes with atomic model building, confirming RPS21 as a 40S component","pmids":["26432834"],"confidence":"Medium","gaps":["No RPS21-specific functional or genetic perturbation performed","Dynamic features attributed to the ribosome as a whole, not to RPS21 in particular"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether the RPS21-containing 40S subunit occupies its structural position within ribosomes engaged in translation inside intact parasites, rather than only in purified preparations, was addressed by imaging ribosomes in situ.","evidence":"In situ cryo-electron tomography of P. falciparum-infected erythrocytes yielding eight high-resolution structures of native translating ribosomes, with and without a Plasmodium-specific translation inhibitor","pmids":["40825879"],"confidence":"Medium","gaps":["RPS21 was visualized only as part of the global 40S subunit; no function was assigned to it","Translation-state and biogenesis changes describe the ribosome broadly, not RPS21 specifically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether RPS21 contributes any specific function to 40S assembly, mRNA/tRNA handling, or translational regulation beyond being a structural constituent of the small subunit remains unaddressed.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout, knockdown, or depletion of RPS21 reported","No interaction or substrate mapping distinguishing RPS21 from the bulk 40S subunit","No evidence for a role in ribosome biogenesis specific to RPS21"],"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":["Established only as a structural component of the P. falciparum 40S small subunit by cryo-EM and in situ cryo-ET; no RPS21-specific function, interaction, or perturbation has been reported in the available corpus."]}},"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":1033,"usd":0.014426,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5783,"output_tokens":1693,"usd":0.03562,"stage2_stop_reason":"end_turn"},"total_usd":0.050046,"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 RPS21 (PF3D7_1144000) is a component of the small (40S) subunit; the structure showed emetine binds the E-site of the small subunit, blocking mRNA/tRNA translocation, establishing the structural context of the 40S ribosomal protein complement including RPS21.\",\n      \"method\": \"Cryo-EM structure determination at 3.2 Å resolution of 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 RPS21 as a structural component of the 40S subunit, but no functional experiment specific to RPS21 itself was performed; finding about RPS21 is incidental to the global ribosome structure\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Five cryo-EM reconstructions of P. falciparum blood-stage schizont ribosomes at sub-nanometer resolution and atomic model building confirmed RPS21 (PF3D7_1144000) as part of the 40S small subunit and revealed structural and dynamic features of the P. falciparum ribosome distinguishing it from mammalian ribosomes.\",\n      \"method\": \"Cryo-EM reconstructions of native ribosomes purified from P. falciparum schizonts; flexible fitting of atomic models into density maps\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — multiple cryo-EM reconstructions with atomic model building confirm RPS21 as a structural component of the small subunit, but no functional experiment specific to RPS21 was performed\",\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, providing molecular-resolution visualization of the 40S subunit (which contains RPS21/PF3D7_1144000) within the native cellular context; translation inhibitor treatment decreased elongation factor-bound ribosomal states and triggered apparent upregulation of ribosome biogenesis.\",\n      \"method\": \"In situ cryo-electron tomography of P. falciparum-infected human erythrocytes; high-resolution structural determination of native ribosomes in translating states with and without a Plasmodium-specific translation inhibitor\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in situ cryo-ET provides high-resolution structural context for RPS21 as part of the native 40S subunit, but no experiment specifically interrogates RPS21 function; finding is incidental to the global ribosome study\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1144000 (RPS21) is established as a structural component of the P. falciparum 40S ribosomal small subunit, as demonstrated by cryo-EM and in situ cryo-ET structures of the native 80S ribosome; beyond its membership in the small subunit, no experiment has established a specific functional, catalytic, or regulatory role for RPS21 itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1144000 (RPS21) is a structural component of the small (40S) subunit of the P. falciparum 80S ribosome, established by cryo-EM structures of the native ribosome that resolved the 40S ribosomal protein complement, including RPS21, and distinguished the parasite ribosome from its mammalian counterpart [#0, #1]. In situ cryo-electron tomography of P. falciparum-infected erythrocytes has since visualized the 40S subunit containing RPS21 within actively translating native ribosomes in the cellular context [#2]. Beyond its membership in the 40S small subunit, no experiment in the available corpus has established a specific catalytic, regulatory, or functional role for RPS21 itself.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether RPS21 is part of the parasite ribosome and how the P. falciparum small subunit is organized was unresolved; a high-resolution structure was needed to place RPS21 within the assembled ribosome.\",\n      \"evidence\": \"Cryo-EM structure at 3.2 Å of the P. falciparum 80S ribosome bound to emetine, resolving the 40S protein complement\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional experiment specific to RPS21 was performed; its role is inferred only from complex membership\",\n        \"Does not establish whether RPS21 has any activity distinct from structural scaffolding\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether the placement of RPS21 in the 40S subunit was robust and how the parasite ribosome differs structurally from the mammalian ribosome required independent reconstructions.\",\n      \"evidence\": \"Multiple cryo-EM reconstructions of native schizont-stage ribosomes with atomic model building, confirming RPS21 as a 40S component\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No RPS21-specific functional or genetic perturbation performed\",\n        \"Dynamic features attributed to the ribosome as a whole, not to RPS21 in particular\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether the RPS21-containing 40S subunit occupies its structural position within ribosomes engaged in translation inside intact parasites, rather than only in purified preparations, was addressed by imaging ribosomes in situ.\",\n      \"evidence\": \"In situ cryo-electron tomography of P. falciparum-infected erythrocytes yielding eight high-resolution structures of native translating ribosomes, with and without a Plasmodium-specific translation inhibitor\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"RPS21 was visualized only as part of the global 40S subunit; no function was assigned to it\",\n        \"Translation-state and biogenesis changes describe the ribosome broadly, not RPS21 specifically\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether RPS21 contributes any specific function to 40S assembly, mRNA/tRNA handling, or translational regulation beyond being a structural constituent of the small subunit remains unaddressed.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout, knockdown, or depletion of RPS21 reported\",\n        \"No interaction or substrate mapping distinguishing RPS21 from the bulk 40S subunit\",\n        \"No evidence for a role in ribosome biogenesis specific to RPS21\"\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      \"Established only as a structural component of the P. falciparum 40S small subunit by cryo-EM and in situ cryo-ET; no RPS21-specific function, interaction, or perturbation has been reported in the available corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1144000","name":null,"product":"40S ribosomal protein S21","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0905000","name":null,"product":"40S ribosomal protein S21, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0941900","name":null,"product":"40S ribosomal protein S21, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPS21","evaluation":null}