{"gene":"PF3D7_1424100","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 solved, revealing the structural context of the large (60S) ribosomal subunit, of which RPL5 (PF3D7_1424100) is a component, bound to emetine at the E-site of the small subunit.","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 80S ribosome establishes structural context for RPL5 as a 60S subunit component, but no findings specific to RPL5 function or interactions are reported beyond its membership in the complex","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 were obtained and atomic models built by flexible fitting, establishing structural features of the 60S subunit (which contains RPL5/PF3D7_1424100) that differentiate the parasite ribosome from mammalian ribosomes.","method":"Cryo-EM reconstruction and atomic model building by flexible fitting","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — multiple cryo-EM reconstructions with atomic model building, but no RPL5-specific mechanistic finding reported; RPL5 is established only as a 60S subunit component","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 with mefloquine bound to the GTPase-associated centre was solved, providing further structural context for the 60S subunit containing RPL5 (PF3D7_1424100); mutagenesis of mefloquine-binding residues confirmed the ribosome as the drug target.","method":"Cryo-EM structure determination at 3.2 Å; site-directed mutagenesis of binding-site residues","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM plus mutagenesis establish ribosome as drug target, but no specific mechanistic finding for RPL5 beyond its membership in the 60S subunit of the complex","pmids":["28288098"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In situ cryo-electron tomography of P. falciparum-infected erythrocytes resolved eight high-resolution structures of the native malarial ribosome in actively translating states, establishing the structural context of the 60S subunit (containing RPL5/PF3D7_1424100) during the translation elongation cycle under physiological conditions.","method":"In situ cryo-electron tomography inside infected erythrocytes","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — rigorous in situ cryo-ET approach with multiple states, but no mechanistic finding specific to RPL5 beyond its membership in the 60S subunit of the translating ribosome","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1424100 (RPL5) is established as a component of the P. falciparum 60S large ribosomal subunit of the 80S cytoplasmic ribosome, whose overall structure has been resolved by cryo-EM and in situ cryo-ET at up to 3.2 Å resolution in multiple translational states; no mechanistic findings specific to RPL5's individual function, interactions, or active-site contributions have been reported beyond its membership in this complex."},"narrative":{"mechanistic_narrative":"PF3D7_1424100 (RPL5) is a component of the large (60S) subunit of the P. falciparum 80S cytoplasmic ribosome, whose structure has been resolved by cryo-EM to 3.2 Å [PMID:24913268] and further characterized across multiple translational states, including in situ within infected erythrocytes during the elongation cycle [PMID:40825879]. Structural comparison of the parasite 60S subunit with mammalian ribosomes has identified features that distinguish the malarial ribosome [PMID:26432834], and the ribosome has been validated as the target of antimalarial drugs including emetine at the small-subunit E-site [PMID:24913268] and mefloquine at the GTPase-associated centre [PMID:28288098]. Beyond its membership in the 60S subunit as defined by these structural studies, no mechanistic function, interaction, or active-site contribution specific to RPL5 has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing the atomic architecture of the P. falciparum ribosome was needed to place RPL5 in a defined structural context; the first high-resolution cryo-EM structure situated RPL5 as a 60S subunit component of the intact 80S ribosome.","evidence":"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å with emetine bound at the small-subunit E-site","pmids":["24913268"],"confidence":"Medium","gaps":["No RPL5-specific function, interaction, or active-site role resolved beyond subunit membership","Emetine binds the small subunit, not RPL5"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To determine whether the parasite ribosome differs from the host, multiple cryo-EM reconstructions were built into atomic models, identifying 60S features that distinguish the malarial ribosome from mammalian ribosomes.","evidence":"Five cryo-EM reconstructions of 80S ribosomes from blood-stage schizonts with atomic model building by flexible fitting","pmids":["26432834"],"confidence":"Medium","gaps":["Distinguishing features not attributed specifically to RPL5","No functional consequence assigned to RPL5"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"To validate the ribosome as an antimalarial drug target, the structure was solved with mefloquine bound and binding-site residues mutated, confirming drug action at the GTPase-associated centre of the 60S-containing ribosome.","evidence":"Cryo-EM at 3.2 Å with mefloquine bound plus site-directed mutagenesis of binding-site residues","pmids":["28288098"],"confidence":"Medium","gaps":["Mefloquine-binding site not attributed to RPL5","No RPL5 involvement in drug binding demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"To capture the ribosome under physiological conditions, in situ cryo-ET resolved actively translating states inside infected erythrocytes, placing the RPL5-containing 60S subunit within the native elongation cycle.","evidence":"In situ cryo-electron tomography of P. falciparum-infected erythrocytes yielding eight high-resolution translating-state structures","pmids":["40825879"],"confidence":"Medium","gaps":["No dynamic or functional role assigned to RPL5 within the elongation cycle","RPL5 characterized only as a structural constituent"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether RPL5 has any function, interaction, or active-site contribution distinct from its structural role in the 60S subunit remains uncharacterized.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No RPL5-specific knockdown, mutagenesis, or interaction study","No assembly or rRNA-binding role established for RPL5","No functional distinction from bulk 60S subunit"],"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":["RPL5 (PF3D7_1424100) is established only as a structural component of the P. falciparum 60S ribosomal subunit; the corpus contains no findings specific to its individual function, interactions, or active-site contributions.","Antimalarial drugs emetine (small-subunit E-site) and mefloquine (GTPase-associated centre) target the ribosome, but neither is attributed to RPL5."]}},"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":4839,"output_tokens":1209,"usd":0.016326,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6038,"output_tokens":1994,"usd":0.04002,"stage2_stop_reason":"end_turn"},"total_usd":0.056346,"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 solved, revealing the structural context of the large (60S) ribosomal subunit, of which RPL5 (PF3D7_1424100) is a component, bound to emetine at the E-site of the small subunit.\",\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 80S ribosome establishes structural context for RPL5 as a 60S subunit component, but no findings specific to RPL5 function or interactions are reported 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\": \"Five cryo-EM reconstructions of P. falciparum 80S ribosomes purified from blood-stage schizonts at sub-nanometer resolution were obtained and atomic models built by flexible fitting, establishing structural features of the 60S subunit (which contains RPL5/PF3D7_1424100) that differentiate the parasite ribosome from mammalian ribosomes.\",\n      \"method\": \"Cryo-EM reconstruction and atomic model building by flexible fitting\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — multiple cryo-EM reconstructions with atomic model building, but no RPL5-specific mechanistic finding reported; RPL5 is established only as a 60S subunit component\",\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 with mefloquine bound to the GTPase-associated centre was solved, providing further structural context for the 60S subunit containing RPL5 (PF3D7_1424100); mutagenesis of mefloquine-binding residues confirmed the ribosome as the drug target.\",\n      \"method\": \"Cryo-EM structure determination at 3.2 Å; site-directed mutagenesis of binding-site residues\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM plus mutagenesis establish ribosome as drug target, but no specific mechanistic finding for RPL5 beyond its membership in the 60S subunit of the complex\",\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 resolved eight high-resolution structures of the native malarial ribosome in actively translating states, establishing the structural context of the 60S subunit (containing RPL5/PF3D7_1424100) during the translation elongation cycle under physiological conditions.\",\n      \"method\": \"In situ cryo-electron tomography inside infected erythrocytes\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — rigorous in situ cryo-ET approach with multiple states, but no mechanistic finding specific to RPL5 beyond its membership in the 60S subunit of the translating ribosome\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1424100 (RPL5) is established as a component of the P. falciparum 60S large ribosomal subunit of the 80S cytoplasmic ribosome, whose overall structure has been resolved by cryo-EM and in situ cryo-ET at up to 3.2 Å resolution in multiple translational states; no mechanistic findings specific to RPL5's individual function, interactions, or active-site contributions have been reported beyond its membership in this complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1424100 (RPL5) is a component of the large (60S) subunit of the P. falciparum 80S cytoplasmic ribosome, whose structure has been resolved by cryo-EM to 3.2 Å [#0] and further characterized across multiple translational states, including in situ within infected erythrocytes during the elongation cycle [#3]. Structural comparison of the parasite 60S subunit with mammalian ribosomes has identified features that distinguish the malarial ribosome [#1], and the ribosome has been validated as the target of antimalarial drugs including emetine at the small-subunit E-site [#0] and mefloquine at the GTPase-associated centre [#2]. Beyond its membership in the 60S subunit as defined by these structural studies, no mechanistic function, interaction, or active-site contribution specific to RPL5 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing the atomic architecture of the P. falciparum ribosome was needed to place RPL5 in a defined structural context; the first high-resolution cryo-EM structure situated RPL5 as a 60S subunit component of the intact 80S ribosome.\",\n      \"evidence\": \"Cryo-EM structure of the P. falciparum 80S ribosome at 3.2 Å with emetine bound at the small-subunit E-site\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No RPL5-specific function, interaction, or active-site role resolved beyond subunit membership\", \"Emetine binds the small subunit, not RPL5\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To determine whether the parasite ribosome differs from the host, multiple cryo-EM reconstructions were built into atomic models, identifying 60S features that distinguish the malarial ribosome from mammalian ribosomes.\",\n      \"evidence\": \"Five cryo-EM reconstructions of 80S ribosomes from blood-stage schizonts with atomic model building by flexible fitting\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Distinguishing features not attributed specifically to RPL5\", \"No functional consequence assigned to RPL5\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"To validate the ribosome as an antimalarial drug target, the structure was solved with mefloquine bound and binding-site residues mutated, confirming drug action at the GTPase-associated centre of the 60S-containing ribosome.\",\n      \"evidence\": \"Cryo-EM at 3.2 Å with mefloquine bound plus site-directed mutagenesis of binding-site residues\",\n      \"pmids\": [\"28288098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mefloquine-binding site not attributed to RPL5\", \"No RPL5 involvement in drug binding demonstrated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To capture the ribosome under physiological conditions, in situ cryo-ET resolved actively translating states inside infected erythrocytes, placing the RPL5-containing 60S subunit within the native elongation cycle.\",\n      \"evidence\": \"In situ cryo-electron tomography of P. falciparum-infected erythrocytes yielding eight high-resolution translating-state structures\",\n      \"pmids\": [\"40825879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No dynamic or functional role assigned to RPL5 within the elongation cycle\", \"RPL5 characterized only as a structural constituent\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether RPL5 has any function, interaction, or active-site contribution distinct from its structural role in the 60S subunit remains uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No RPL5-specific knockdown, mutagenesis, or interaction study\", \"No assembly or rRNA-binding role established for RPL5\", \"No functional distinction from bulk 60S subunit\"],\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, 3]}\n    ],\n    \"complexes\": [\n      \"60S large ribosomal subunit of the P. falciparum 80S cytoplasmic ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"RPL5 (PF3D7_1424100) is established only as a structural component of the P. falciparum 60S ribosomal subunit; the corpus contains no findings specific to its individual function, interactions, or active-site contributions.\",\n      \"Antimalarial drugs emetine (small-subunit E-site) and mefloquine (GTPase-associated centre) target the ribosome, but neither is attributed to RPL5.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1424100","name":null,"product":"60S ribosomal protein L5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1019500","name":null,"product":"60S ribosomal protein L5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1333800","name":null,"product":"60S ribosomal protein L5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPL5","evaluation":null}