{"gene":"PF3D7_1130100","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2014,"finding":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution was solved, revealing the structural context of ribosomal proteins including RPL38 (PF3D7_1130100) as a component of the large (60S) subunit within the intact 80S complex bound to emetine.","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 whole ribosome establishes RPL38 membership in the 60S subunit but provides no specific functional data for RPL38 itself beyond complex membership","pmids":["24913268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Five cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts at sub-nanometer resolution established atomic models of the complex, confirming RPL38 (PF3D7_1130100) as a structural constituent of the 60S large subunit in the parasite ribosome.","method":"Cryo-EM reconstruction with flexible-fitting atomic model building","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — multiple cryo-EM reconstructions establish ribosome structure but provide no specific functional or mechanistic data for RPL38 individually","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution with mefloquine bound to the GTPase-associated centre further confirmed RPL38 (PF3D7_1130100) as a component of the 60S subunit of the parasite ribosome involved in protein synthesis.","method":"Cryo-EM structure determination at 3.2 Å resolution; mutagenesis of binding-site residues","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — rigorous cryo-EM plus mutagenesis confirms ribosome structure but no specific mechanistic data unique to RPL38 beyond its presence in the 60S subunit","pmids":["28288098"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In situ cryo-electron tomography of P. falciparum-infected erythrocytes produced eight high-resolution structures of the native malarial ribosome in actively translating states, establishing RPL38 (PF3D7_1130100) as a component of the 60S subunit within the physiologically active 80S ribosome in the native cellular context.","method":"In situ cryo-electron tomography inside infected erythrocytes; integrated structural biology","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — state-of-the-art in-cell cryo-ET establishes ribosome complex membership in native context but delivers no RPL38-specific mechanistic data","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1130100 (RPL38) is established as a structural component of the 60S large subunit of the P. falciparum 80S cytoplasmic ribosome, as shown by multiple cryo-EM and cryo-ET structures of the intact ribosomal complex; no RPL38-specific enzymatic activity, binding partners, post-translational modifications, or individual functional roles beyond complex membership have been mechanistically characterized in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_1130100 (RPL38) is a structural component of the 60S large subunit of the P. falciparum 80S cytoplasmic ribosome, identified as a constituent of the intact ribosomal complex by successive high-resolution cryo-EM structures of the parasite ribosome [PMID:24913268, PMID:26432834]. It has been resolved within the 80S ribosome in complexes bound to translation-inhibiting ligands such as emetine and mefloquine [PMID:24913268, PMID:28288098], and within the physiologically active, translating ribosome imaged in situ inside infected erythrocytes by cryo-electron tomography [PMID:40825879]. Beyond its membership in the 60S subunit as established by these structural studies, no RPL38-specific enzymatic activity, binding partners, post-translational modifications, or individual functional role has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Whether RPL38 is a resolvable structural constituent of the P. falciparum ribosome was first addressed by placing it within the atomic architecture of the 80S complex.","evidence":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å bound to emetine","pmids":["24913268"],"confidence":"Medium","gaps":["No RPL38-specific function or activity established beyond 60S subunit membership","No binding partners or post-translational modifications identified","Contribution of RPL38 to translation or ribosome assembly not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Multiple independent reconstructions from blood-stage schizonts confirmed RPL38 as a consistent structural constituent of the 60S subunit rather than a variably occupied position.","evidence":"Five cryo-EM reconstructions with flexible-fitting atomic model building from schizont-purified ribosomes","pmids":["26432834"],"confidence":"Medium","gaps":["Does not address RPL38's individual role in subunit assembly or function","No stage-specific or condition-dependent behavior of RPL38 examined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Structural placement of RPL38 was reaffirmed in a ribosome captured with an antimalarial ligand at the GTPase-associated centre, situating the protein within the translationally competent particle.","evidence":"Cryo-EM at 3.2 Å with mefloquine bound and mutagenesis of binding-site residues","pmids":["28288098"],"confidence":"Medium","gaps":["Mutagenesis targeted the drug-binding site, not RPL38 itself","No direct link between RPL38 and the ligand-binding or catalytic function shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether the structural assignment holds in the native cellular context, rather than in purified particles, was resolved by imaging actively translating ribosomes in situ.","evidence":"In situ cryo-electron tomography inside infected erythrocytes yielding eight structures of the native translating ribosome","pmids":["40825879"],"confidence":"Medium","gaps":["Confirms native complex membership but assigns no RPL38-specific mechanistic role","No functional perturbation of RPL38 tested in the native context"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether RPL38 has any function specific to itself beyond serving as a structural building block of the 60S subunit.","evidence":"No experiment isolating RPL38 activity, interactions, or perturbation phenotype is present in the corpus","pmids":[],"confidence":"Medium","gaps":["No genetic knockdown/knockout phenotype for RPL38 reported","No RPL38-specific binding partners or extraribosomal roles characterized","No post-translational modifications or regulatory features identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["60S large ribosomal subunit of the P. falciparum 80S cytoplasmic ribosome"],"partners":[],"other_free_text":["RPL38 (PF3D7_1130100) is characterized in the available corpus only as a structural constituent of the 60S subunit; no function, interaction, or modification specific to the protein itself has been established.","RPL38 has been resolved in ribosomes bound to the antimalarial ligands emetine [#0] and mefloquine [#2], but no direct role of RPL38 in ligand binding was demonstrated."]}},"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":"28288098","id":"PMC_28288098","title":"Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis.","date":"2017","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28288098","citation_count":138,"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":4836,"output_tokens":1142,"usd":0.015819,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5957,"output_tokens":1996,"usd":0.039843,"stage2_stop_reason":"end_turn"},"total_usd":0.055662,"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\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution was solved, revealing the structural context of ribosomal proteins including RPL38 (PF3D7_1130100) as a component of the large (60S) subunit within the intact 80S complex bound to emetine.\",\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 whole ribosome establishes RPL38 membership in the 60S subunit but provides no specific functional data for RPL38 itself beyond complex membership\",\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 80S ribosomes purified from blood-stage schizonts at sub-nanometer resolution established atomic models of the complex, confirming RPL38 (PF3D7_1130100) as a structural constituent of the 60S large subunit in the parasite ribosome.\",\n      \"method\": \"Cryo-EM reconstruction with flexible-fitting atomic model building\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — multiple cryo-EM reconstructions establish ribosome structure but provide no specific functional or mechanistic data for RPL38 individually\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å resolution with mefloquine bound to the GTPase-associated centre further confirmed RPL38 (PF3D7_1130100) as a component of the 60S subunit of the parasite ribosome involved in protein synthesis.\",\n      \"method\": \"Cryo-EM structure determination at 3.2 Å resolution; mutagenesis of binding-site residues\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — rigorous cryo-EM plus mutagenesis confirms ribosome structure but no specific mechanistic data unique to RPL38 beyond its presence in the 60S subunit\",\n      \"pmids\": [\"28288098\"],\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 produced eight high-resolution structures of the native malarial ribosome in actively translating states, establishing RPL38 (PF3D7_1130100) as a component of the 60S subunit within the physiologically active 80S ribosome in the native cellular context.\",\n      \"method\": \"In situ cryo-electron tomography inside infected erythrocytes; integrated structural biology\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — state-of-the-art in-cell cryo-ET establishes ribosome complex membership in native context but delivers no RPL38-specific mechanistic data\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1130100 (RPL38) is established as a structural component of the 60S large subunit of the P. falciparum 80S cytoplasmic ribosome, as shown by multiple cryo-EM and cryo-ET structures of the intact ribosomal complex; no RPL38-specific enzymatic activity, binding partners, post-translational modifications, or individual functional roles beyond complex membership have been mechanistically characterized in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1130100 (RPL38) is a structural component of the 60S large subunit of the P. falciparum 80S cytoplasmic ribosome, identified as a constituent of the intact ribosomal complex by successive high-resolution cryo-EM structures of the parasite ribosome [#0, #1]. It has been resolved within the 80S ribosome in complexes bound to translation-inhibiting ligands such as emetine and mefloquine [#0, #2], and within the physiologically active, translating ribosome imaged in situ inside infected erythrocytes by cryo-electron tomography [#3]. Beyond its membership in the 60S subunit as established by these structural studies, no RPL38-specific enzymatic activity, binding partners, post-translational modifications, or individual functional role has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether RPL38 is a resolvable structural constituent of the P. falciparum ribosome was first addressed by placing it within the atomic architecture of the 80S complex.\",\n      \"evidence\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å bound to emetine\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No RPL38-specific function or activity established beyond 60S subunit membership\",\n        \"No binding partners or post-translational modifications identified\",\n        \"Contribution of RPL38 to translation or ribosome assembly not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Multiple independent reconstructions from blood-stage schizonts confirmed RPL38 as a consistent structural constituent of the 60S subunit rather than a variably occupied position.\",\n      \"evidence\": \"Five cryo-EM reconstructions with flexible-fitting atomic model building from schizont-purified ribosomes\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not address RPL38's individual role in subunit assembly or function\",\n        \"No stage-specific or condition-dependent behavior of RPL38 examined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Structural placement of RPL38 was reaffirmed in a ribosome captured with an antimalarial ligand at the GTPase-associated centre, situating the protein within the translationally competent particle.\",\n      \"evidence\": \"Cryo-EM at 3.2 Å with mefloquine bound and mutagenesis of binding-site residues\",\n      \"pmids\": [\"28288098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mutagenesis targeted the drug-binding site, not RPL38 itself\",\n        \"No direct link between RPL38 and the ligand-binding or catalytic function shown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether the structural assignment holds in the native cellular context, rather than in purified particles, was resolved by imaging actively translating ribosomes in situ.\",\n      \"evidence\": \"In situ cryo-electron tomography inside infected erythrocytes yielding eight structures of the native translating ribosome\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Confirms native complex membership but assigns no RPL38-specific mechanistic role\",\n        \"No functional perturbation of RPL38 tested in the native context\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether RPL38 has any function specific to itself beyond serving as a structural building block of the 60S subunit.\",\n      \"evidence\": \"No experiment isolating RPL38 activity, interactions, or perturbation phenotype is present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No genetic knockdown/knockout phenotype for RPL38 reported\",\n        \"No RPL38-specific binding partners or extraribosomal roles characterized\",\n        \"No post-translational modifications or regulatory features identified\"\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, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0022625\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"complexes\": [\n      \"60S large ribosomal subunit of the P. falciparum 80S cytoplasmic ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"RPL38 (PF3D7_1130100) is characterized in the available corpus only as a structural constituent of the 60S subunit; no function, interaction, or modification specific to the protein itself has been established.\",\n      \"RPL38 has been resolved in ribosomes bound to the antimalarial ligands emetine [#0] and mefloquine [#2], but no direct role of RPL38 in ligand binding was demonstrated.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1130100","name":null,"product":"60S ribosomal protein L38","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0918100","name":null,"product":"60S ribosomal protein L38, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0928000","name":null,"product":"60S ribosomal protein L38, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPL38","evaluation":null}