{"gene":"PF3D7_1447000","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 small subunit (40S) architecture including ribosomal proteins such as S5 (PF3D7_1447000) as part of the complex bound to emetine at the E-site; emetine blocks mRNA/tRNA translocation by interacting with the small subunit E-site.","method":"Cryo-EM structure determination at 3.2 Å resolution of the P. falciparum 80S ribosome in complex with emetine","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — atomic-resolution cryo-EM structure of the whole ribosome complex; S5/PF3D7_1447000 is implicitly present as a 40S subunit component but is not individually characterized or functionally probed in this study","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, with atomic models built by flexible fitting; S5 (PF3D7_1447000) is a constituent 40S subunit protein visualized within these structures, revealing structural and dynamic features that differentiate the P. falciparum ribosome from mammalian ribosomes.","method":"Cryo-EM reconstruction with flexible-fitting atomic model building from blood-stage schizont-purified ribosomes","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM with atomic models, but S5/PF3D7_1447000 is not individually functionally characterized; finding is its presence as a structural component of the 40S subunit","pmids":["26432834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"A 3.2 Å cryo-EM structure of the P. falciparum 80S ribosome with (+)-mefloquine bound to the GTPase-associated centre was solved; S5 (PF3D7_1447000) is a structural component of the 40S subunit present in this complex. Mutagenesis of mefloquine-binding residues generated parasites with increased resistance, confirming the ribosome as the drug target.","method":"Cryo-EM structure at 3.2 Å; site-directed mutagenesis of binding residues; parasite resistance assay","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — rigorous structural and mutagenesis study of the intact 80S complex; S5/PF3D7_1447000 is present as a 40S component but is not individually probed or mutated","pmids":["28288098"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Eight high-resolution in situ cryo-ET structures of the native P. falciparum 80S ribosome in actively translating states inside infected erythrocytes were determined; S5 (PF3D7_1447000) is a 40S subunit component present in these structures, which revealed new molecular details of the malarial translation elongation cycle and drug-induced structural changes.","method":"In situ cryo-electron tomography (cryo-ET) of P. falciparum-infected erythrocytes; high-resolution structure determination of actively translating ribosomes","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in-cell atomic-resolution cryo-ET, multiple states; S5/PF3D7_1447000 is a structural component of the 40S subunit but is not individually characterized","pmids":["40825879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Artemisinin treatment was shown to stabilize PfRACK1 binding to the P. falciparum 80S ribosome; structural analysis revealed that the r-protein uS3 (a different 40S subunit protein) in Plasmodium has a truncated C-terminal tail compared to most eukaryotes, preventing its interaction with RACK1. S5 (PF3D7_1447000) is a 40S subunit member present in the ribosomal complex studied but is not individually characterized in this study.","method":"Cryo-EM structural analysis of artemisinin-treated P. falciparum ribosomes; structural comparison of ribosomal protein uS3 C-terminal tail","journal":"Structure (London, England : 1993)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — S5/PF3D7_1447000 is a passive structural component of the 80S complex studied; no specific experiment targets or characterizes S5 itself","pmids":["40480224"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"P. falciparum cytoplasmic ribosomes (containing 40S subunit components including S5/PF3D7_1447000) were shown by cryo-EM to bind both the open PfAlu domain and the closed human Alu domain of the signal recognition particle with nanomolar affinity, demonstrating non-discriminative SRP Alu domain recognition by the P. falciparum ribosome.","method":"Cryo-EM and binding affinity measurements (NMR, SAXS, cryo-EM) of P. falciparum ribosomes with SRP Alu domains","journal":"Communications biology","confidence":"Low","confidence_rationale":"Tier 2 / Weak — direct binding experiment with the intact ribosome complex; S5/PF3D7_1447000 is a 40S subunit constituent but is not individually characterized in this interaction study","pmids":["34017052"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"MAP-X (meltome-assisted profiling of protein complexes via thermal proteome profiling in intact cells) applied across seven timepoints of the P. falciparum intraerythrocytic developmental cycle predicted PF3D7_1447000 (S5) as part of the ribosomal protein complex, revealing dynamic alterations in complex composition across blood stages.","method":"Thermal proteome profiling (MAP-X) in intact P. falciparum cells across IDC timepoints; proteome-wide protein complex mapping","journal":"Nature microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — pan-complex proteomics approach; S5/PF3D7_1447000 membership in the ribosome is inferred from co-melting profiles, single method, no functional validation of S5 specifically","pmids":["41315737"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1447000 (40S ribosomal protein S5) is established as a structural component of the P. falciparum 40S small ribosomal subunit, present in multiple high-resolution cryo-EM and in situ cryo-ET structures of the actively translating P. falciparum 80S ribosome; beyond its membership in this complex and its visualization in ribosome structures used to study drug binding (emetine, mefloquine) and translational dynamics, no specific mechanistic function, interaction, or post-translational modification has been individually demonstrated for S5/PF3D7_1447000 in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_1447000 (S5) is a structural component of the 40S small ribosomal subunit of the Plasmodium falciparum 80S ribosome, present in multiple high-resolution cryo-EM structures of the assembled translating ribosome [PMID:24913268, PMID:26432834]. It has been visualized as a constituent 40S protein in ribosome complexes used to define the parasite's translation machinery and its distinguishing features from mammalian ribosomes, including structures with the translation inhibitors emetine bound at the small-subunit E-site [PMID:24913268] and (+)-mefloquine bound at the GTPase-associated centre [PMID:28288098], and in in situ cryo-ET reconstructions of actively translating ribosomes inside infected erythrocytes [PMID:40825879]. Beyond its membership in the 40S subunit of the P. falciparum ribosome, no specific molecular function, direct interaction, substrate, or post-translational modification has been individually demonstrated for S5/PF3D7_1447000 in the available corpus; in every structural and proteomic study it appears as a passive component of the larger ribosomal complex rather than being individually probed [PMID:40480224, PMID:34017052, PMID:41315737].","teleology":[{"year":2014,"claim":"Establishing the architecture of the P. falciparum 40S subunit answered where S5 physically sits within the assembled ribosome and placed it in a drug-relevant complex.","evidence":"3.2 Å cryo-EM structure of the P. falciparum 80S ribosome bound to emetine at the small-subunit E-site","pmids":["24913268"],"confidence":"Medium","gaps":["S5 itself is not functionally probed or mutated","no S5-specific interaction with emetine demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Multiple sub-nanometer reconstructions from blood-stage schizonts confirmed S5 as a stable constituent of the 40S subunit and captured dynamic states distinguishing the parasite ribosome from the mammalian one.","evidence":"Cryo-EM reconstructions with flexible-fitting atomic model building from schizont-purified ribosomes","pmids":["26432834"],"confidence":"Medium","gaps":["S5 not individually functionally characterized","role of S5 in the observed dynamics not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"A drug-bound structure with mutagenesis validation confirmed the ribosome as an antimalarial target, with S5 present as a 40S component of the targeted complex.","evidence":"3.2 Å cryo-EM of the 80S ribosome with (+)-mefloquine and site-directed mutagenesis of binding residues plus parasite resistance assay","pmids":["28288098"],"confidence":"Medium","gaps":["mefloquine binds the GTPase-associated centre, not S5","S5 residues were not mutated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Characterizing ribosome–SRP Alu domain recognition tested how the intact parasite ribosome, of which S5 is a part, engages the translation regulatory machinery.","evidence":"Cryo-EM plus NMR/SAXS binding affinity measurements of P. falciparum ribosomes with open and closed SRP Alu domains","pmids":["34017052"],"confidence":"Low","gaps":["binding is a whole-ribosome property; no S5-specific contribution shown","S5 not individually characterized in the interaction"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"In situ cryo-ET and drug-response structural studies extended the picture to actively translating ribosomes in cells, with S5 present across states of the elongation cycle.","evidence":"In situ cryo-ET of infected erythrocytes across translation states, and cryo-EM of artemisinin-treated ribosomes examining RACK1 and uS3","pmids":["40825879","40480224"],"confidence":"Medium","gaps":["artemisinin/RACK1 effects centre on uS3, not S5","no S5-specific structural change reported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Proteome-wide complex mapping across the intraerythrocytic cycle independently assigned S5 to the ribosomal protein complex and hinted at stage-dependent compositional dynamics.","evidence":"Thermal proteome profiling (MAP-X) in intact cells across seven IDC timepoints","pmids":["41315737"],"confidence":"Low","gaps":["membership inferred from co-melting profiles only","no functional validation specific to S5","stage-specific role of S5 not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether S5/PF3D7_1447000 has any function beyond structural incorporation into the 40S subunit — a direct partner, a role in mRNA/tRNA positioning, or a distinct contribution to translation regulation or drug response — remains unaddressed.","evidence":"No study in the corpus individually probes S5","pmids":[],"confidence":"Low","gaps":["no S5-specific knockdown or mutation","no direct S5 interactor identified","no S5-specific post-translational modification characterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["P. falciparum 40S small ribosomal subunit","P. falciparum 80S ribosome"],"partners":[],"other_free_text":["S5/PF3D7_1447000 appears only as a structural constituent of the 40S subunit within the intact 80S ribosome; no S5-specific direct interaction partner is established in the corpus.","Ribosome complexes containing S5 have been characterized as targets of the antimalarials emetine (E-site) [#0] and (+)-mefloquine (GTPase-associated centre) [#2], but the drug-binding sites are not on S5.","Artemisinin-stabilized RACK1 binding and the truncated uS3 C-terminal tail involve a different 40S protein (uS3), not S5 [#4]."]}},"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 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},{"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":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":"29903714","id":"PMC_29903714","title":"New Insights into Ribosome Structure and Function.","date":"2019","source":"Cold Spring Harbor perspectives in biology","url":"https://pubmed.ncbi.nlm.nih.gov/29903714","citation_count":48,"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":"31481454","id":"PMC_31481454","title":"Extensions, Extra Factors, and Extreme Complexity: Ribosomal Structures Provide Insights into Eukaryotic Translation.","date":"2019","source":"Cold Spring Harbor perspectives in biology","url":"https://pubmed.ncbi.nlm.nih.gov/31481454","citation_count":26,"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":"28138066","id":"PMC_28138066","title":"The translation elongation cycle-capturing multiple states by cryo-electron microscopy.","date":"2017","source":"Philosophical transactions of the Royal Society of London. 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emetine blocks mRNA/tRNA translocation by interacting with the small subunit E-site.\",\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\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — atomic-resolution cryo-EM structure of the whole ribosome complex; S5/PF3D7_1447000 is implicitly present as a 40S subunit component but is not individually characterized or functionally probed in this study\",\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, with atomic models built by flexible fitting; S5 (PF3D7_1447000) is a constituent 40S subunit protein visualized within these structures, revealing structural and dynamic features that differentiate the P. falciparum ribosome from mammalian ribosomes.\",\n      \"method\": \"Cryo-EM reconstruction with flexible-fitting atomic model building from blood-stage schizont-purified ribosomes\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM with atomic models, but S5/PF3D7_1447000 is not individually functionally characterized; finding is its presence as a structural component of the 40S subunit\",\n      \"pmids\": [\"26432834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"A 3.2 Å cryo-EM structure of the P. falciparum 80S ribosome with (+)-mefloquine bound to the GTPase-associated centre was solved; S5 (PF3D7_1447000) is a structural component of the 40S subunit present in this complex. Mutagenesis of mefloquine-binding residues generated parasites with increased resistance, confirming the ribosome as the drug target.\",\n      \"method\": \"Cryo-EM structure at 3.2 Å; site-directed mutagenesis of binding residues; parasite resistance assay\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — rigorous structural and mutagenesis study of the intact 80S complex; S5/PF3D7_1447000 is present as a 40S component but is not individually probed or mutated\",\n      \"pmids\": [\"28288098\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Eight high-resolution in situ cryo-ET structures of the native P. falciparum 80S ribosome in actively translating states inside infected erythrocytes were determined; S5 (PF3D7_1447000) is a 40S subunit component present in these structures, which revealed new molecular details of the malarial translation elongation cycle and drug-induced structural changes.\",\n      \"method\": \"In situ cryo-electron tomography (cryo-ET) of P. falciparum-infected erythrocytes; high-resolution structure determination of actively translating ribosomes\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in-cell atomic-resolution cryo-ET, multiple states; S5/PF3D7_1447000 is a structural component of the 40S subunit but is not individually characterized\",\n      \"pmids\": [\"40825879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Artemisinin treatment was shown to stabilize PfRACK1 binding to the P. falciparum 80S ribosome; structural analysis revealed that the r-protein uS3 (a different 40S subunit protein) in Plasmodium has a truncated C-terminal tail compared to most eukaryotes, preventing its interaction with RACK1. S5 (PF3D7_1447000) is a 40S subunit member present in the ribosomal complex studied but is not individually characterized in this study.\",\n      \"method\": \"Cryo-EM structural analysis of artemisinin-treated P. falciparum ribosomes; structural comparison of ribosomal protein uS3 C-terminal tail\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — S5/PF3D7_1447000 is a passive structural component of the 80S complex studied; no specific experiment targets or characterizes S5 itself\",\n      \"pmids\": [\"40480224\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"P. falciparum cytoplasmic ribosomes (containing 40S subunit components including S5/PF3D7_1447000) were shown by cryo-EM to bind both the open PfAlu domain and the closed human Alu domain of the signal recognition particle with nanomolar affinity, demonstrating non-discriminative SRP Alu domain recognition by the P. falciparum ribosome.\",\n      \"method\": \"Cryo-EM and binding affinity measurements (NMR, SAXS, cryo-EM) of P. falciparum ribosomes with SRP Alu domains\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct binding experiment with the intact ribosome complex; S5/PF3D7_1447000 is a 40S subunit constituent but is not individually characterized in this interaction study\",\n      \"pmids\": [\"34017052\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MAP-X (meltome-assisted profiling of protein complexes via thermal proteome profiling in intact cells) applied across seven timepoints of the P. falciparum intraerythrocytic developmental cycle predicted PF3D7_1447000 (S5) as part of the ribosomal protein complex, revealing dynamic alterations in complex composition across blood stages.\",\n      \"method\": \"Thermal proteome profiling (MAP-X) in intact P. falciparum cells across IDC timepoints; proteome-wide protein complex mapping\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — pan-complex proteomics approach; S5/PF3D7_1447000 membership in the ribosome is inferred from co-melting profiles, single method, no functional validation of S5 specifically\",\n      \"pmids\": [\"41315737\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1447000 (40S ribosomal protein S5) is established as a structural component of the P. falciparum 40S small ribosomal subunit, present in multiple high-resolution cryo-EM and in situ cryo-ET structures of the actively translating P. falciparum 80S ribosome; beyond its membership in this complex and its visualization in ribosome structures used to study drug binding (emetine, mefloquine) and translational dynamics, no specific mechanistic function, interaction, or post-translational modification has been individually demonstrated for S5/PF3D7_1447000 in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1447000 (S5) is a structural component of the 40S small ribosomal subunit of the Plasmodium falciparum 80S ribosome, present in multiple high-resolution cryo-EM structures of the assembled translating ribosome [#0, #1]. It has been visualized as a constituent 40S protein in ribosome complexes used to define the parasite's translation machinery and its distinguishing features from mammalian ribosomes, including structures with the translation inhibitors emetine bound at the small-subunit E-site [#0] and (+)-mefloquine bound at the GTPase-associated centre [#2], and in in situ cryo-ET reconstructions of actively translating ribosomes inside infected erythrocytes [#3]. Beyond its membership in the 40S subunit of the P. falciparum ribosome, no specific molecular function, direct interaction, substrate, or post-translational modification has been individually demonstrated for S5/PF3D7_1447000 in the available corpus; in every structural and proteomic study it appears as a passive component of the larger ribosomal complex rather than being individually probed [#4, #5, #6].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing the architecture of the P. falciparum 40S subunit answered where S5 physically sits within the assembled ribosome and placed it in a drug-relevant complex.\",\n      \"evidence\": \"3.2 Å cryo-EM structure of the P. falciparum 80S ribosome bound to emetine at the small-subunit E-site\",\n      \"pmids\": [\"24913268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"S5 itself is not functionally probed or mutated\", \"no S5-specific interaction with emetine demonstrated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Multiple sub-nanometer reconstructions from blood-stage schizonts confirmed S5 as a stable constituent of the 40S subunit and captured dynamic states distinguishing the parasite ribosome from the mammalian one.\",\n      \"evidence\": \"Cryo-EM reconstructions with flexible-fitting atomic model building from schizont-purified ribosomes\",\n      \"pmids\": [\"26432834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"S5 not individually functionally characterized\", \"role of S5 in the observed dynamics not addressed\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"A drug-bound structure with mutagenesis validation confirmed the ribosome as an antimalarial target, with S5 present as a 40S component of the targeted complex.\",\n      \"evidence\": \"3.2 Å cryo-EM of the 80S ribosome with (+)-mefloquine and site-directed mutagenesis of binding residues plus parasite resistance assay\",\n      \"pmids\": [\"28288098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"mefloquine binds the GTPase-associated centre, not S5\", \"S5 residues were not mutated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Characterizing ribosome–SRP Alu domain recognition tested how the intact parasite ribosome, of which S5 is a part, engages the translation regulatory machinery.\",\n      \"evidence\": \"Cryo-EM plus NMR/SAXS binding affinity measurements of P. falciparum ribosomes with open and closed SRP Alu domains\",\n      \"pmids\": [\"34017052\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"binding is a whole-ribosome property; no S5-specific contribution shown\", \"S5 not individually characterized in the interaction\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"In situ cryo-ET and drug-response structural studies extended the picture to actively translating ribosomes in cells, with S5 present across states of the elongation cycle.\",\n      \"evidence\": \"In situ cryo-ET of infected erythrocytes across translation states, and cryo-EM of artemisinin-treated ribosomes examining RACK1 and uS3\",\n      \"pmids\": [\"40825879\", \"40480224\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"artemisinin/RACK1 effects centre on uS3, not S5\", \"no S5-specific structural change reported\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Proteome-wide complex mapping across the intraerythrocytic cycle independently assigned S5 to the ribosomal protein complex and hinted at stage-dependent compositional dynamics.\",\n      \"evidence\": \"Thermal proteome profiling (MAP-X) in intact cells across seven IDC timepoints\",\n      \"pmids\": [\"41315737\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"membership inferred from co-melting profiles only\", \"no functional validation specific to S5\", \"stage-specific role of S5 not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether S5/PF3D7_1447000 has any function beyond structural incorporation into the 40S subunit — a direct partner, a role in mRNA/tRNA positioning, or a distinct contribution to translation regulation or drug response — remains unaddressed.\",\n      \"evidence\": \"No study in the corpus individually probes S5\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"no S5-specific knockdown or mutation\", \"no direct S5 interactor identified\", \"no S5-specific post-translational modification characterized\"],\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, 6]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006414\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"P. falciparum 40S small ribosomal subunit\",\n      \"P. falciparum 80S ribosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"S5/PF3D7_1447000 appears only as a structural constituent of the 40S subunit within the intact 80S ribosome; no S5-specific direct interaction partner is established in the corpus.\",\n      \"Ribosome complexes containing S5 have been characterized as targets of the antimalarials emetine (E-site) [#0] and (+)-mefloquine (GTPase-associated centre) [#2], but the drug-binding sites are not on S5.\",\n      \"Artemisinin-stabilized RACK1 binding and the truncated uS3 C-terminal tail involve a different 40S protein (uS3), not S5 [#4].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1447000","name":null,"product":"40S ribosomal protein S5","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1310800","name":null,"product":"40S ribosomal protein S5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1235200","name":null,"product":"40S ribosomal protein S5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}