{"gene":"PF3D7_1365100","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2020,"finding":"PfmtRPS17 (PF3D7_1365100) localizes to the mitochondrion of P. falciparum, as verified by immuno-EM, where the mitoribosome is closely associated with the mitochondrial inner membrane.","method":"CRISPR/Cas9-based conditional knockdown combined with immuno-electron microscopy","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immuno-EM with functional knockdown, single lab, two orthogonal methods (immuno-EM + conditional knockdown)","pmids":["32273345"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Conditional knockdown of PfmtRPS17 (PF3D7_1365100) is lethal to P. falciparum, establishing its essentiality for parasite viability and confirming its role as a bona fide small mitoribosomal subunit protein.","method":"CRISPR/Cas9-based conditional knockdown with parasite growth/viability readout","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional knockdown with defined viability phenotype, single lab","pmids":["32273345"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Knockdown of PfmtRPS17 (PF3D7_1365100) renders P. falciparum hypersensitive to inhibitors of mitochondrial Complex III (bc1), dihydroorotate dehydrogenase (DHODH), and F1F0-ATP synthase, indicating that the mitoribosome (and PfmtRPS17 as its component) is required to sustain mitochondrial electron transport chain function.","method":"Conditional knockdown followed by differential drug sensitivity assays (IC50 determination)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional phenotype via conditional knockdown with pharmacological readout, single lab","pmids":["32273345"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Knockdown of PfmtRPS17 (PF3D7_1365100) blocks the pyrimidine de novo biosynthesis pathway and reduces the cellular pool of pyrimidine nucleotides, demonstrating that the P. falciparum mitoribosome is required to maintain the metabolic capacity of the mitochondrion needed to support DHODH-dependent pyrimidine synthesis.","method":"Conditional knockdown combined with metabolomics profiling of pyrimidine pathway intermediates","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with metabolomics readout, single lab, two orthogonal methods","pmids":["32273345"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfmtRPS17 (PF3D7_1365100) is an essential component of the small subunit of the P. falciparum mitoribosome that localizes to the mitochondrial inner membrane; its loss disrupts mitochondrial translation, collapses the mitochondrial electron transport chain function, impairs de novo pyrimidine biosynthesis, and renders parasites hypersensitive to mitochondria-targeting drugs."},"narrative":{"mechanistic_narrative":"PfmtRPS17 (PF3D7_1365100) is an essential component of the small subunit of the P. falciparum mitoribosome that localizes to the parasite mitochondrion, where the mitoribosome is closely associated with the mitochondrial inner membrane [PMID:32273345]. Conditional knockdown of PfmtRPS17 is lethal, establishing its essentiality for parasite viability and confirming its role as a bona fide small mitoribosomal subunit protein [PMID:32273345]. Loss of PfmtRPS17 function compromises mitochondrial physiology: knockdown parasites become hypersensitive to inhibitors of Complex III (bc1), dihydroorotate dehydrogenase (DHODH), and F1F0-ATP synthase, indicating the mitoribosome is required to sustain electron transport chain function [PMID:32273345], and it blocks de novo pyrimidine biosynthesis with depletion of pyrimidine nucleotide pools, linking mitoribosome activity to the DHODH-dependent metabolic output of the mitochondrion [PMID:32273345]. Beyond its role as a small mitoribosomal subunit protein defined by these knockdown phenotypes, no further molecular detail of PfmtRPS17 itself (e.g. structure, direct RNA or protein contacts) has been characterized in the available corpus.","teleology":[{"year":2020,"claim":"Whether PF3D7_1365100 encodes a genuine mitochondrial component was unknown; establishing its subcellular home was the prerequisite for assigning it to the mitoribosome.","evidence":"immuno-electron microscopy combined with CRISPR/Cas9 conditional knockdown in P. falciparum","pmids":["32273345"],"confidence":"Medium","gaps":["Direct demonstration of PfmtRPS17 incorporation into an assembled small subunit particle (e.g. by density gradient or structure) is not shown","Single lab, two orthogonal methods only","RNA or protein binding partners of PfmtRPS17 within the mitoribosome not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"It was unclear whether PfmtRPS17 is dispensable or required; conditional knockdown showed loss is lethal, establishing essentiality for parasite viability and its identity as a functional mitoribosomal protein.","evidence":"CRISPR/Cas9 conditional knockdown with parasite growth/viability readout","pmids":["32273345"],"confidence":"Medium","gaps":["Whether lethality stems from a general translation defect versus a specific role of PfmtRPS17 is not resolved","Single lab observation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To connect mitoribosome activity to downstream mitochondrial function, knockdown was combined with pharmacology, showing hypersensitivity to Complex III, DHODH, and ATP synthase inhibitors and thus a requirement for sustaining electron transport chain function.","evidence":"conditional knockdown followed by differential drug sensitivity (IC50) assays","pmids":["32273345"],"confidence":"Medium","gaps":["Which mitochondrially encoded ETC subunits become limiting upon knockdown is not mapped","Direct measurement of mitochondrial translation output not provided"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"The metabolic consequence of mitoribosome loss was defined by showing knockdown blocks de novo pyrimidine biosynthesis and depletes pyrimidine nucleotide pools, tying PfmtRPS17 function to DHODH-dependent metabolism.","evidence":"conditional knockdown with metabolomics profiling of pyrimidine pathway intermediates","pmids":["32273345"],"confidence":"Medium","gaps":["Causal chain from mitoribosome loss to DHODH inactivity (via ETC/ubiquinone) is inferred rather than directly measured","Single lab observation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The molecular architecture of PfmtRPS17 within the small mitoribosomal subunit — its structure, RNA contacts, assembly partners, and any function distinct from its complex membership — remains uncharacterized.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model or resolved contacts for PfmtRPS17","No identified direct interaction partners specific to PfmtRPS17","Assembly pathway of the P. falciparum small mitoribosomal subunit not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["small subunit of the P. falciparum mitochondrial ribosome (mitoribosome)"],"partners":[],"other_free_text":["Conditional knockdown is lethal to P. falciparum, indicating essentiality [#1]","Knockdown confers hypersensitivity to Complex III (bc1), DHODH, and F1F0-ATP synthase inhibitors [#2]","Knockdown blocks de novo pyrimidine biosynthesis and depletes pyrimidine nucleotide pools [#3]","All characterization derives from a single study in P. falciparum; no molecular detail of PfmtRPS17 beyond its mitoribosomal membership and knockdown phenotypes is present in the corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32273345","id":"PMC_32273345","title":"Genetic ablation of the mitoribosome in the malaria parasite Plasmodium falciparum sensitizes it to antimalarials that target mitochondrial functions.","date":"2020","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/32273345","citation_count":30,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["S17","PfmtRPS17"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35277503","id":"","title":"Functional genomics of RAP proteins and their role in mitoribosome regulation in Plasmodium falciparum.","date":"2022","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/35277503","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["mtRPS17"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4529,"output_tokens":1063,"usd":0.014766,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5895,"output_tokens":2328,"usd":0.043838,"stage2_stop_reason":"end_turn"},"total_usd":0.058604,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"PfmtRPS17 (PF3D7_1365100) localizes to the mitochondrion of P. falciparum, as verified by immuno-EM, where the mitoribosome is closely associated with the mitochondrial inner membrane.\",\n      \"method\": \"CRISPR/Cas9-based conditional knockdown combined with immuno-electron microscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immuno-EM with functional knockdown, single lab, two orthogonal methods (immuno-EM + conditional knockdown)\",\n      \"pmids\": [\"32273345\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Conditional knockdown of PfmtRPS17 (PF3D7_1365100) is lethal to P. falciparum, establishing its essentiality for parasite viability and confirming its role as a bona fide small mitoribosomal subunit protein.\",\n      \"method\": \"CRISPR/Cas9-based conditional knockdown with parasite growth/viability readout\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional knockdown with defined viability phenotype, single lab\",\n      \"pmids\": [\"32273345\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Knockdown of PfmtRPS17 (PF3D7_1365100) renders P. falciparum hypersensitive to inhibitors of mitochondrial Complex III (bc1), dihydroorotate dehydrogenase (DHODH), and F1F0-ATP synthase, indicating that the mitoribosome (and PfmtRPS17 as its component) is required to sustain mitochondrial electron transport chain function.\",\n      \"method\": \"Conditional knockdown followed by differential drug sensitivity assays (IC50 determination)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional phenotype via conditional knockdown with pharmacological readout, single lab\",\n      \"pmids\": [\"32273345\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Knockdown of PfmtRPS17 (PF3D7_1365100) blocks the pyrimidine de novo biosynthesis pathway and reduces the cellular pool of pyrimidine nucleotides, demonstrating that the P. falciparum mitoribosome is required to maintain the metabolic capacity of the mitochondrion needed to support DHODH-dependent pyrimidine synthesis.\",\n      \"method\": \"Conditional knockdown combined with metabolomics profiling of pyrimidine pathway intermediates\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with metabolomics readout, single lab, two orthogonal methods\",\n      \"pmids\": [\"32273345\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfmtRPS17 (PF3D7_1365100) is an essential component of the small subunit of the P. falciparum mitoribosome that localizes to the mitochondrial inner membrane; its loss disrupts mitochondrial translation, collapses the mitochondrial electron transport chain function, impairs de novo pyrimidine biosynthesis, and renders parasites hypersensitive to mitochondria-targeting drugs.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PfmtRPS17 (PF3D7_1365100) is an essential component of the small subunit of the P. falciparum mitoribosome that localizes to the parasite mitochondrion, where the mitoribosome is closely associated with the mitochondrial inner membrane [#0]. Conditional knockdown of PfmtRPS17 is lethal, establishing its essentiality for parasite viability and confirming its role as a bona fide small mitoribosomal subunit protein [#1]. Loss of PfmtRPS17 function compromises mitochondrial physiology: knockdown parasites become hypersensitive to inhibitors of Complex III (bc1), dihydroorotate dehydrogenase (DHODH), and F1F0-ATP synthase, indicating the mitoribosome is required to sustain electron transport chain function [#2], and it blocks de novo pyrimidine biosynthesis with depletion of pyrimidine nucleotide pools, linking mitoribosome activity to the DHODH-dependent metabolic output of the mitochondrion [#3]. Beyond its role as a small mitoribosomal subunit protein defined by these knockdown phenotypes, no further molecular detail of PfmtRPS17 itself (e.g. structure, direct RNA or protein contacts) has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether PF3D7_1365100 encodes a genuine mitochondrial component was unknown; establishing its subcellular home was the prerequisite for assigning it to the mitoribosome.\",\n      \"evidence\": \"immuno-electron microscopy combined with CRISPR/Cas9 conditional knockdown in P. falciparum\",\n      \"pmids\": [\"32273345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct demonstration of PfmtRPS17 incorporation into an assembled small subunit particle (e.g. by density gradient or structure) is not shown\",\n        \"Single lab, two orthogonal methods only\",\n        \"RNA or protein binding partners of PfmtRPS17 within the mitoribosome not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"It was unclear whether PfmtRPS17 is dispensable or required; conditional knockdown showed loss is lethal, establishing essentiality for parasite viability and its identity as a functional mitoribosomal protein.\",\n      \"evidence\": \"CRISPR/Cas9 conditional knockdown with parasite growth/viability readout\",\n      \"pmids\": [\"32273345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether lethality stems from a general translation defect versus a specific role of PfmtRPS17 is not resolved\",\n        \"Single lab observation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To connect mitoribosome activity to downstream mitochondrial function, knockdown was combined with pharmacology, showing hypersensitivity to Complex III, DHODH, and ATP synthase inhibitors and thus a requirement for sustaining electron transport chain function.\",\n      \"evidence\": \"conditional knockdown followed by differential drug sensitivity (IC50) assays\",\n      \"pmids\": [\"32273345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Which mitochondrially encoded ETC subunits become limiting upon knockdown is not mapped\",\n        \"Direct measurement of mitochondrial translation output not provided\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The metabolic consequence of mitoribosome loss was defined by showing knockdown blocks de novo pyrimidine biosynthesis and depletes pyrimidine nucleotide pools, tying PfmtRPS17 function to DHODH-dependent metabolism.\",\n      \"evidence\": \"conditional knockdown with metabolomics profiling of pyrimidine pathway intermediates\",\n      \"pmids\": [\"32273345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Causal chain from mitoribosome loss to DHODH inactivity (via ETC/ubiquinone) is inferred rather than directly measured\",\n        \"Single lab observation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular architecture of PfmtRPS17 within the small mitoribosomal subunit — its structure, RNA contacts, assembly partners, and any function distinct from its complex membership — remains uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model or resolved contacts for PfmtRPS17\",\n        \"No identified direct interaction partners specific to PfmtRPS17\",\n        \"Assembly pathway of the P. falciparum small mitoribosomal subunit not established\"\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]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0032543\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0006207\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"small subunit of the P. falciparum mitochondrial ribosome (mitoribosome)\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Conditional knockdown is lethal to P. falciparum, indicating essentiality [#1]\",\n      \"Knockdown confers hypersensitivity to Complex III (bc1), DHODH, and F1F0-ATP synthase inhibitors [#2]\",\n      \"Knockdown blocks de novo pyrimidine biosynthesis and depletes pyrimidine nucleotide pools [#3]\",\n      \"All characterization derives from a single study in P. falciparum; no molecular detail of PfmtRPS17 beyond its mitoribosomal membership and knockdown phenotypes is present in the corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1365100","name":null,"product":"ribosomal protein S17, mitochondrial","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1140900","name":null,"product":"ribosomal protein S17, mitochondrial, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1106200","name":null,"product":"ribosomal protein S17, mitochondrial, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"mtRPS17","evaluation":null}