{"gene":"PF3D7_0305000","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2010,"finding":"Recombinant P. falciparum EF-Ts (PF3D7_0305000) mediates nucleotide exchange on apicoplast-encoded EF-Tu, promoting GDP release; homology modeling of the EF-Tu:EF-Ts complex revealed EF-Ts-induced structural alterations that expedite GDP release from EF-Tu.","method":"In vitro nucleotide exchange assay with recombinant proteins; homology modeling of the EF-Tu:EF-Ts complex","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical reconstitution of nucleotide exchange activity, single lab, no independent replication","pmids":["21163263"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"The predicted leader sequence of P. falciparum EF-Ts (PF3D7_0305000) targeted GFP to the apicoplast, confirming that EF-Ts localizes to and functions in this organelle.","method":"GFP fusion reporter assay with fluorescence microscopy to track apicoplast targeting","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment with GFP reporter, single lab, single method","pmids":["21163263"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"Recombinant P. falciparum EF-Ts (PF3D7_0305000) physically interacts with apicoplast-encoded EF-Tu, establishing a functional complex between two translation elongation factors encoded in different cellular compartments (nuclear vs. plastid genome).","method":"Protein-protein interaction assay with recombinant proteins (pulldown/binding assay implied by GTP hydrolysis and nucleotide exchange functional characterization)","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional interaction demonstrated in vitro, single lab, single study","pmids":["21163263"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum EF-Ts (PF3D7_0305000) is a nuclear-encoded apicoplast-targeted translation elongation factor whose N-terminal leader sequence directs it to the apicoplast, where it functions as a guanine nucleotide exchange factor by binding apicoplast-encoded EF-Tu and catalyzing GDP release to regenerate the active EF-Tu·GTP complex required for protein translation in the plastid."},"narrative":{"mechanistic_narrative":"PF3D7_0305000 (EF-Ts) is a nuclear-encoded apicoplast translation factor of Plasmodium falciparum that regenerates the active form of the apicoplast elongation factor EF-Tu [PMID:21163263]. Its N-terminal leader sequence directs the protein to the apicoplast, as demonstrated by GFP-reporter targeting [PMID:21163263]. Within this organelle, recombinant EF-Ts physically binds the apicoplast-genome-encoded EF-Tu and catalyzes GDP release from it, acting as a guanine nucleotide exchange factor that couples the two elongation factors across compartmental (nuclear vs. plastid) genome boundaries [PMID:21163263]. Beyond in vitro reconstitution of this nucleotide-exchange activity and its apicoplast localization, no further mechanistic detail — including in vivo genetic requirement or structural characterization of the complex — has been established in the available corpus.","teleology":[{"year":2010,"claim":"Whether the nuclear-encoded EF-Ts partners functionally with the plastid-encoded EF-Tu was unknown; demonstrating direct binding established a cross-compartment translation elongation complex.","evidence":"In vitro protein-protein interaction assay with recombinant P. falciparum EF-Ts and apicoplast-encoded EF-Tu","pmids":["21163263"],"confidence":"Medium","gaps":["Interaction shown only in vitro with recombinant proteins; no in vivo confirmation of the complex","Binding interface and stoichiometry not resolved experimentally","No reciprocal validation across independent methods"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"The catalytic role of EF-Ts was undefined; nucleotide-exchange assays showed it promotes GDP release from EF-Tu, establishing it as a guanine nucleotide exchange factor that regenerates active EF-Tu.","evidence":"In vitro nucleotide exchange assay with recombinant proteins, supported by homology modeling of the EF-Tu:EF-Ts complex","pmids":["21163263"],"confidence":"Medium","gaps":["Single-lab in vitro reconstitution without independent replication","Structural basis inferred from homology modeling rather than an experimental structure","Kinetics and physiological rate of exchange in the intact apicoplast not measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"The subcellular site of EF-Ts action was unknown; its predicted leader sequence directed a GFP reporter to the apicoplast, placing its function within this organelle's translation machinery.","evidence":"GFP fusion reporter assay with fluorescence microscopy tracking apicoplast targeting","pmids":["21163263"],"confidence":"Medium","gaps":["Localization inferred from a leader-sequence GFP fusion, not the full-length endogenous protein","Single method in a single lab","Import processing and mature protein topology within the apicoplast not characterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether EF-Ts is genetically required for apicoplast translation and parasite viability, and how its exchange activity is regulated in vivo, remains unaddressed.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No knockout, knockdown, or conditional-depletion phenotype reported","No experimental structure of the P. falciparum EF-Tu:EF-Ts complex","Essentiality and drug-target potential in the apicoplast not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["EF-Tu:EF-Ts elongation factor complex (apicoplast)"],"partners":["APICOPLAST-ENCODED EF-TU"],"other_free_text":["Nuclear-encoded, apicoplast-targeted via an N-terminal leader sequence","Acts as guanine nucleotide exchange factor promoting GDP release from EF-Tu"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"21163263","id":"PMC_21163263","title":"Interaction of apicoplast-encoded elongation factor (EF) EF-Tu with nuclear-encoded EF-Ts mediates translation in the Plasmodiumfalciparum plastid.","date":"2010","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/21163263","citation_count":17,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EF-Ts"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35444689","id":"","title":"In-Silico Functional Annotation of Plasmodium falciparum Hypothetical Proteins to Identify Novel Drug Targets.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35444689","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EF-Ts"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26555664","id":"","title":"Tetracyclines in malaria.","date":"2015","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/26555664","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EF-Ts"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5992,"output_tokens":833,"usd":0.015236,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5521,"output_tokens":1876,"usd":0.037253,"stage2_stop_reason":"end_turn"},"total_usd":0.052489,"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\": 2010,\n      \"finding\": \"Recombinant P. falciparum EF-Ts (PF3D7_0305000) mediates nucleotide exchange on apicoplast-encoded EF-Tu, promoting GDP release; homology modeling of the EF-Tu:EF-Ts complex revealed EF-Ts-induced structural alterations that expedite GDP release from EF-Tu.\",\n      \"method\": \"In vitro nucleotide exchange assay with recombinant proteins; homology modeling of the EF-Tu:EF-Ts complex\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical reconstitution of nucleotide exchange activity, single lab, no independent replication\",\n      \"pmids\": [\"21163263\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The predicted leader sequence of P. falciparum EF-Ts (PF3D7_0305000) targeted GFP to the apicoplast, confirming that EF-Ts localizes to and functions in this organelle.\",\n      \"method\": \"GFP fusion reporter assay with fluorescence microscopy to track apicoplast targeting\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment with GFP reporter, single lab, single method\",\n      \"pmids\": [\"21163263\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Recombinant P. falciparum EF-Ts (PF3D7_0305000) physically interacts with apicoplast-encoded EF-Tu, establishing a functional complex between two translation elongation factors encoded in different cellular compartments (nuclear vs. plastid genome).\",\n      \"method\": \"Protein-protein interaction assay with recombinant proteins (pulldown/binding assay implied by GTP hydrolysis and nucleotide exchange functional characterization)\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional interaction demonstrated in vitro, single lab, single study\",\n      \"pmids\": [\"21163263\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"P. falciparum EF-Ts (PF3D7_0305000) is a nuclear-encoded apicoplast-targeted translation elongation factor whose N-terminal leader sequence directs it to the apicoplast, where it functions as a guanine nucleotide exchange factor by binding apicoplast-encoded EF-Tu and catalyzing GDP release to regenerate the active EF-Tu·GTP complex required for protein translation in the plastid.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0305000 (EF-Ts) is a nuclear-encoded apicoplast translation factor of Plasmodium falciparum that regenerates the active form of the apicoplast elongation factor EF-Tu [#0, #2]. Its N-terminal leader sequence directs the protein to the apicoplast, as demonstrated by GFP-reporter targeting [#1]. Within this organelle, recombinant EF-Ts physically binds the apicoplast-genome-encoded EF-Tu and catalyzes GDP release from it, acting as a guanine nucleotide exchange factor that couples the two elongation factors across compartmental (nuclear vs. plastid) genome boundaries [#0, #2]. Beyond in vitro reconstitution of this nucleotide-exchange activity and its apicoplast localization, no further mechanistic detail — including in vivo genetic requirement or structural characterization of the complex — has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Whether the nuclear-encoded EF-Ts partners functionally with the plastid-encoded EF-Tu was unknown; demonstrating direct binding established a cross-compartment translation elongation complex.\",\n      \"evidence\": \"In vitro protein-protein interaction assay with recombinant P. falciparum EF-Ts and apicoplast-encoded EF-Tu\",\n      \"pmids\": [\"21163263\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Interaction shown only in vitro with recombinant proteins; no in vivo confirmation of the complex\",\n        \"Binding interface and stoichiometry not resolved experimentally\",\n        \"No reciprocal validation across independent methods\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"The catalytic role of EF-Ts was undefined; nucleotide-exchange assays showed it promotes GDP release from EF-Tu, establishing it as a guanine nucleotide exchange factor that regenerates active EF-Tu.\",\n      \"evidence\": \"In vitro nucleotide exchange assay with recombinant proteins, supported by homology modeling of the EF-Tu:EF-Ts complex\",\n      \"pmids\": [\"21163263\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single-lab in vitro reconstitution without independent replication\",\n        \"Structural basis inferred from homology modeling rather than an experimental structure\",\n        \"Kinetics and physiological rate of exchange in the intact apicoplast not measured\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"The subcellular site of EF-Ts action was unknown; its predicted leader sequence directed a GFP reporter to the apicoplast, placing its function within this organelle's translation machinery.\",\n      \"evidence\": \"GFP fusion reporter assay with fluorescence microscopy tracking apicoplast targeting\",\n      \"pmids\": [\"21163263\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Localization inferred from a leader-sequence GFP fusion, not the full-length endogenous protein\",\n        \"Single method in a single lab\",\n        \"Import processing and mature protein topology within the apicoplast not characterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether EF-Ts is genetically required for apicoplast translation and parasite viability, and how its exchange activity is regulated in vivo, remains unaddressed.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No knockout, knockdown, or conditional-depletion phenotype reported\",\n        \"No experimental structure of the P. falciparum EF-Tu:EF-Ts complex\",\n        \"Essentiality and drug-target potential in the apicoplast not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003746\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005085\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006414\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\n      \"EF-Tu:EF-Ts elongation factor complex (apicoplast)\"\n    ],\n    \"partners\": [\n      \"apicoplast-encoded EF-Tu\"\n    ],\n    \"other_free_text\": [\n      \"Nuclear-encoded, apicoplast-targeted via an N-terminal leader sequence\",\n      \"Acts as guanine nucleotide exchange factor promoting GDP release from EF-Tu\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0305000","name":null,"product":"elongation factor Ts","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0403500","name":null,"product":"elongation factor (EF-TS), putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0838100","name":null,"product":"elongation factor (EF-TS), putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"EF-Ts","evaluation":null}