{"gene":"PF3D7_1465900","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2014,"finding":"The cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution places the 40S ribosomal protein S3 (PF3D7_1465900) as a structural component of the small ribosomal subunit, visualized as part of the intact ribosome complex.","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 ribosome establishes S3's structural position, but no functional experiments were performed specifically on S3; single study","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Cryo-EM reconstructions of the P. falciparum 80S ribosome purified from blood-stage schizonts further confirm S3 (PF3D7_1465900) as a structural component of the small subunit; atomic models were built from density maps by flexible fitting.","method":"Cryo-EM with flexible fitting to build atomic models","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — independent replication of ribosome structure with atomic model building, but no functional characterization specific to S3","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In artemisinin-treated P. falciparum, structural analysis revealed that PfRACK1 does not interact with the C-terminal tail of the r-protein uS3 (PF3D7_1465900) because this tail is truncated in Plasmodium compared to most eukaryotes, suggesting an evolved difference in RACK1-ribosome interaction that may affect translational regulation.","method":"Cryo-EM structural analysis of artemisinin-treated P. falciparum ribosomes; comparative structural analysis of uS3 C-terminal tail","journal":"Structure (London, England : 1993)","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — cryo-EM structural observation in a single study; the truncation of the uS3 C-terminal tail is structurally established but functional consequences for S3 itself are inferred, not directly tested","pmids":["40480224"],"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, placing S3 (PF3D7_1465900) as a structural component of the small subunit within the cellular context; drug-induced perturbation altered elongation-factor-bound ribosomal states.","method":"In situ cryo-electron tomography inside P. falciparum-infected human erythrocytes","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — highest-resolution in-cell structural data, but mechanistic findings specific to S3 itself are not distinguished from the overall ribosome complex; single study","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1465900 (S3/uS3) is established as a structural component of the P. falciparum 40S ribosomal small subunit, resolved in multiple cryo-EM structures; its C-terminal tail is truncated relative to other eukaryotes, abolishing the conserved interaction with PfRACK1 that is mediated by this tail in most eukaryotes, but no independent enzymatic or functional experiments specific to S3 itself have been reported."},"narrative":{"mechanistic_narrative":"PF3D7_1465900 (S3/uS3) is a structural component of the 40S small subunit of the Plasmodium falciparum ribosome, resolved as an integral part of the intact 80S ribosome across multiple independent cryo-EM studies of blood-stage parasites [PMID:24913268, PMID:26432834] and in native, actively translating states captured by in situ cryo-electron tomography inside infected erythrocytes [PMID:40825879]. Structural comparison shows that the C-terminal tail of uS3 is truncated in Plasmodium relative to most eukaryotes, so PfRACK1 does not engage this tail as it does in other species, marking an evolved divergence in the RACK1–ribosome interface [PMID:40480224]. Beyond its assignment as a small-subunit structural protein and this observed tail truncation, no enzymatic or functional experiments specific to S3 itself have been characterized in the available corpus; its individual contribution to translation, translational regulation, or drug response is inferred only from its position within the ribosome complex.","teleology":[{"year":2014,"claim":"Establishing where S3 sits in the parasite ribosome addressed whether it is a bona fide structural component of the small subunit, anchoring all later functional interpretation.","evidence":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution","pmids":["24913268"],"confidence":"Medium","gaps":["No functional experiment performed on S3 itself","Role in translation initiation, elongation, or fidelity not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Independent reconstruction from schizont-derived ribosomes confirmed S3's small-subunit assignment with an atomic model, reinforcing the structural placement.","evidence":"Cryo-EM with flexible fitting to build atomic models from blood-stage schizont ribosomes","pmids":["26432834"],"confidence":"Medium","gaps":["Still no S3-specific functional assay","Stage-specific or non-ribosomal roles not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Comparative structural analysis addressed how S3 participates in the RACK1–ribosome interface, revealing that its C-terminal tail is truncated in Plasmodium so PfRACK1 does not bind it as in other eukaryotes.","evidence":"Cryo-EM structural analysis of artemisinin-treated P. falciparum ribosomes with comparative analysis of the uS3 C-terminal tail","pmids":["40480224"],"confidence":"Medium","gaps":["Functional consequence of the tail truncation for S3 is inferred, not directly tested","Effect on translational regulation not experimentally demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"In-cell structural determination placed S3 within natively translating ribosomes, confirming its position in the cellular context and linking ribosomal states to drug perturbation.","evidence":"In situ cryo-electron tomography inside P. falciparum-infected human erythrocytes, yielding eight high-resolution translating-state structures","pmids":["40825879"],"confidence":"Medium","gaps":["S3-specific mechanistic contribution not distinguished from the whole ribosome","Drug-induced changes attributed to elongation-factor states, not to S3 directly"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether S3's truncated C-terminal tail and loss of the PfRACK1 interaction confer any parasite-specific translational or drug-response function remains untested by direct experiment.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genetic knockdown, knockout, or complementation of S3","No reconstitution of the S3–RACK1 interface","No biochemical assay isolating S3 function from the ribosome"],"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":["C-terminal tail of uS3 (PF3D7_1465900) is truncated in P. falciparum relative to most eukaryotes, abolishing the conserved PfRACK1 interaction mediated by this tail in other species [#2]","No enzymatic or functional experiment specific to S3 itself has been reported; its role is established only through structural membership in the ribosome"]}},"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 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microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28288098","citation_count":136,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32469313","id":"PMC_32469313","title":"Plasmodium falciparum translational machinery condones polyadenosine repeats.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/32469313","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37053161","id":"PMC_37053161","title":"Ribosome heterogeneity and specialization of Plasmodium parasites.","date":"2023","source":"PLoS 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biology","url":"https://pubmed.ncbi.nlm.nih.gov/34017052","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35452681","id":"PMC_35452681","title":"Association of the receptor for activated C-kinase 1 with ribosomes in Plasmodium falciparum.","date":"2022","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35452681","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41315737","id":"PMC_41315737","title":"MAP-X reveals distinct protein complex dynamics across Plasmodium falciparum blood stages.","date":"2025","source":"Nature 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vectors","url":"https://pubmed.ncbi.nlm.nih.gov/42001110","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7751,"output_tokens":1151,"usd":0.020259,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5940,"output_tokens":1923,"usd":0.038887,"stage2_stop_reason":"end_turn"},"total_usd":0.059146,"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\": \"The cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution places the 40S ribosomal protein S3 (PF3D7_1465900) as a structural component of the small ribosomal subunit, visualized as part of the intact ribosome complex.\",\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 ribosome establishes S3's structural position, but no functional experiments were performed specifically on S3; single study\",\n      \"pmids\": [\"24913268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Cryo-EM reconstructions of the P. falciparum 80S ribosome purified from blood-stage schizonts further confirm S3 (PF3D7_1465900) as a structural component of the small subunit; atomic models were built from density maps by flexible fitting.\",\n      \"method\": \"Cryo-EM with flexible fitting to build atomic models\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — independent replication of ribosome structure with atomic model building, but no functional characterization specific to S3\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In artemisinin-treated P. falciparum, structural analysis revealed that PfRACK1 does not interact with the C-terminal tail of the r-protein uS3 (PF3D7_1465900) because this tail is truncated in Plasmodium compared to most eukaryotes, suggesting an evolved difference in RACK1-ribosome interaction that may affect translational regulation.\",\n      \"method\": \"Cryo-EM structural analysis of artemisinin-treated P. falciparum ribosomes; comparative structural analysis of uS3 C-terminal tail\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — cryo-EM structural observation in a single study; the truncation of the uS3 C-terminal tail is structurally established but functional consequences for S3 itself are inferred, not directly tested\",\n      \"pmids\": [\"40480224\"],\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, placing S3 (PF3D7_1465900) as a structural component of the small subunit within the cellular context; drug-induced perturbation altered elongation-factor-bound ribosomal states.\",\n      \"method\": \"In situ cryo-electron tomography inside P. falciparum-infected human erythrocytes\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — highest-resolution in-cell structural data, but mechanistic findings specific to S3 itself are not distinguished from the overall ribosome complex; single study\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1465900 (S3/uS3) is established as a structural component of the P. falciparum 40S ribosomal small subunit, resolved in multiple cryo-EM structures; its C-terminal tail is truncated relative to other eukaryotes, abolishing the conserved interaction with PfRACK1 that is mediated by this tail in most eukaryotes, but no independent enzymatic or functional experiments specific to S3 itself have been reported.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1465900 (S3/uS3) is a structural component of the 40S small subunit of the Plasmodium falciparum ribosome, resolved as an integral part of the intact 80S ribosome across multiple independent cryo-EM studies of blood-stage parasites [#0, #1] and in native, actively translating states captured by in situ cryo-electron tomography inside infected erythrocytes [#3]. Structural comparison shows that the C-terminal tail of uS3 is truncated in Plasmodium relative to most eukaryotes, so PfRACK1 does not engage this tail as it does in other species, marking an evolved divergence in the RACK1–ribosome interface [#2]. Beyond its assignment as a small-subunit structural protein and this observed tail truncation, no enzymatic or functional experiments specific to S3 itself have been characterized in the available corpus; its individual contribution to translation, translational regulation, or drug response is inferred only from its position within the ribosome complex.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing where S3 sits in the parasite ribosome addressed whether it is a bona fide structural component of the small subunit, anchoring all later functional interpretation.\",\n      \"evidence\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional experiment performed on S3 itself\", \"Role in translation initiation, elongation, or fidelity not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Independent reconstruction from schizont-derived ribosomes confirmed S3's small-subunit assignment with an atomic model, reinforcing the structural placement.\",\n      \"evidence\": \"Cryo-EM with flexible fitting to build atomic models from blood-stage schizont ribosomes\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Still no S3-specific functional assay\", \"Stage-specific or non-ribosomal roles not addressed\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Comparative structural analysis addressed how S3 participates in the RACK1–ribosome interface, revealing that its C-terminal tail is truncated in Plasmodium so PfRACK1 does not bind it as in other eukaryotes.\",\n      \"evidence\": \"Cryo-EM structural analysis of artemisinin-treated P. falciparum ribosomes with comparative analysis of the uS3 C-terminal tail\",\n      \"pmids\": [\"40480224\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the tail truncation for S3 is inferred, not directly tested\", \"Effect on translational regulation not experimentally demonstrated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"In-cell structural determination placed S3 within natively translating ribosomes, confirming its position in the cellular context and linking ribosomal states to drug perturbation.\",\n      \"evidence\": \"In situ cryo-electron tomography inside P. falciparum-infected human erythrocytes, yielding eight high-resolution translating-state structures\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"S3-specific mechanistic contribution not distinguished from the whole ribosome\", \"Drug-induced changes attributed to elongation-factor states, not to S3 directly\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether S3's truncated C-terminal tail and loss of the PfRACK1 interaction confer any parasite-specific translational or drug-response function remains untested by direct experiment.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No genetic knockdown, knockout, or complementation of S3\", \"No reconstitution of the S3–RACK1 interface\", \"No biochemical assay isolating S3 function from the ribosome\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003735\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0022627\", \"supporting_discovery_ids\": [0, 1, 2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"40S small ribosomal subunit (P. falciparum)\",\n      \"80S ribosome (P. falciparum)\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"C-terminal tail of uS3 (PF3D7_1465900) is truncated in P. falciparum relative to most eukaryotes, abolishing the conserved PfRACK1 interaction mediated by this tail in other species [#2]\",\n      \"No enzymatic or functional experiment specific to S3 itself has been reported; its role is established only through structural membership in the ribosome\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1465900","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 2 of 4 cited papers name other catalogue genes (PF3D7_0826700). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1465900","name":null,"product":"40S ribosomal protein S3","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1329300","name":null,"product":"40S ribosomal protein S3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1215600","name":null,"product":"40S ribosomal protein S3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}