{"gene":"PF3D7_1012300","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2024,"finding":"QCR7 (PF3D7_1012300) was specifically enriched by a photoactivatable derivative of 9-methoxystrobilurin G (9MG) in chemoproteomic-based target profiling, identifying it as a component of mitochondrial complex III physically accessible to this compound in P. falciparum.","method":"Chemoproteomic target profiling using a photoactivatable derivative of 9MG (activity-based protein profiling / photo-crosslinking enrichment)","journal":"Molecular omics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, single chemoproteomic method; enrichment is consistent with complex III membership but does not establish direct binding to QCR7 specifically vs. indirect co-enrichment","pmids":["39262389"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2021,"finding":"QCR7 (PF3D7_1012300) co-migrates with cytochrome bc1 complex (Complex III) subunits at an apparent molecular mass of ~730 kDa by complexome profiling, establishing its membership in the P. falciparum CIII dimer that also includes CYTB, CYTC1, the Rieske subunit, QCR9, QCR8, MPPα, MPPβ, and novel Apicomplexa-specific subunits C3AP1–3.","method":"Complexome profiling (blue-native PAGE fractionation coupled to quantitative mass spectrometry) across asexual blood stages and gametocytes","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — complexome profiling with quantitative MS across two life stages; co-migration across multiple fractions provides robust evidence of complex membership","pmids":["34155201"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"QCR7 (PF3D7_1012300) is stabilised by atovaquone treatment in P. falciparum lysates as detected by solvent proteome profiling (SPP), confirming its physical association within mitochondrial Complex III that is the target of atovaquone.","method":"Solvent-induced proteome profiling (SPP) — differential protein stability analysis by mass spectrometry comparing atovaquone vs. DMSO conditions","journal":"International journal for parasitology. Drugs and drug resistance","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, single proteomics-based method; stabilisation is consistent with complex membership but does not pinpoint a direct drug-binding role for QCR7","pmids":["41308470"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"QCR7 (PF3D7_1012300) is a subunit of the P. falciparum mitochondrial cytochrome bc1 complex (Complex III), co-migrating with CYTB, CYTC1, the Rieske subunit, QCR8, QCR9, MPPα/β, and novel Apicomplexa-specific subunits in a ~730 kDa dimer; it is physically enriched by a photoactivatable analog of the antimalarial 9-methoxystrobilurin G and is stabilised by atovaquone treatment, consistent with its integral role in Complex III function, but no catalytic activity or direct binding mechanism has been experimentally defined for QCR7 itself."},"narrative":{"mechanistic_narrative":"QCR7 (PF3D7_1012300) is a subunit of the P. falciparum mitochondrial cytochrome bc1 complex (Complex III), identified through its co-migration at ~730 kDa with the CIII dimer components CYTB, CYTC1, the Rieske subunit, QCR8, QCR9, MPPα/β, and Apicomplexa-specific subunits by complexome profiling [PMID:34155201]. Its physical association within this complex is corroborated by chemoproteomic enrichment with a photoactivatable derivative of the antimalarial 9-methoxystrobilurin G [PMID:39262389] and by atovaquone-induced stabilisation in solvent proteome profiling [PMID:41308470], both consistent with membership in the drug-targeted Complex III. Beyond establishing QCR7 as a constituent of Complex III, the available corpus defines no catalytic activity, direct drug-binding role, or independent function for QCR7 itself.","teleology":[{"year":2021,"claim":"Establishing which proteins constitute the P. falciparum Complex III was needed to define the parasite's respiratory chain organization; complexome profiling placed QCR7 within the CIII dimer.","evidence":"Blue-native PAGE fractionation coupled to quantitative mass spectrometry across asexual blood stages and gametocytes, showing co-migration at ~730 kDa","pmids":["34155201"],"confidence":"High","gaps":["Co-migration establishes complex membership but not a specific structural or catalytic role for QCR7","No stoichiometry or direct interaction partner within the complex is resolved for QCR7","No structural model of QCR7 in the assembled complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Whether QCR7 is physically accessible to Complex III-targeting antimalarials was unknown; chemoproteomic profiling showed a 9MG-derived probe enriches QCR7.","evidence":"Chemoproteomic target profiling using a photoactivatable derivative of 9-methoxystrobilurin G (photo-crosslinking enrichment) in P. falciparum 3D7","pmids":["39262389"],"confidence":"Medium","gaps":["Single lab, single chemoproteomic method; enrichment does not distinguish direct probe binding to QCR7 from indirect co-enrichment via the complex","No binding site on QCR7 identified","No functional consequence of probe engagement demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2025,"claim":"Whether QCR7 responds to atovaquone, the canonical Complex III inhibitor, was untested; solvent proteome profiling showed QCR7 is stabilised by atovaquone treatment.","evidence":"Solvent-induced proteome profiling (differential protein stability by mass spectrometry) comparing atovaquone vs. DMSO in P. falciparum lysates","pmids":["41308470"],"confidence":"Medium","gaps":["Single lab, single proteomics method; stabilisation reflects complex association rather than a direct QCR7 drug-binding role","Does not define whether QCR7 contributes to atovaquone sensitivity or resistance","No mechanistic link between stabilisation and QCR7 function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The intrinsic molecular function of QCR7 within Complex III, its direct interaction partners, and any independent contribution to electron transfer or complex assembly remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No catalytic activity or biochemical role assigned to QCR7 itself","No direct binding mechanism to any inhibitor established for QCR7","No genetic knockdown/knockout phenotype characterized for QCR7 in the corpus"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial cytochrome bc1 complex (Complex III) ~730 kDa dimer"],"partners":["CYTB","CYTC1","RIESKE SUBUNIT","QCR8","QCR9","MPPΑ","MPPΒ","C3AP1-3 (APICOMPLEXA-SPECIFIC SUBUNITS)"],"other_free_text":["Enriched by a photoactivatable derivative of the antimalarial 9-methoxystrobilurin G [#0]","Stabilised by atovaquone treatment in solvent proteome profiling [#2]","No catalytic activity or direct drug-binding mechanism defined for QCR7 itself in the corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"39262389","id":"PMC_39262389","title":"Antimalarial mechanism of action of the natural product 9-methoxystrobilurin G.","date":"2024","source":"Molecular omics","url":"https://pubmed.ncbi.nlm.nih.gov/39262389","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["QCR7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41308470","id":"","title":"Validation of solvent proteome profiling for antimalarial drug target deconvolution.","date":"2025","source":"International journal for parasitology. Drugs and drug resistance","url":"https://pubmed.ncbi.nlm.nih.gov/41308470","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["QCR7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34155201","id":"","title":"Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34155201","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["QCR7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6029,"output_tokens":1020,"usd":0.016694,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5792,"output_tokens":2008,"usd":0.03958,"stage2_stop_reason":"end_turn"},"total_usd":0.056274,"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\": 2024,\n      \"finding\": \"QCR7 (PF3D7_1012300) was specifically enriched by a photoactivatable derivative of 9-methoxystrobilurin G (9MG) in chemoproteomic-based target profiling, identifying it as a component of mitochondrial complex III physically accessible to this compound in P. falciparum.\",\n      \"method\": \"Chemoproteomic target profiling using a photoactivatable derivative of 9MG (activity-based protein profiling / photo-crosslinking enrichment)\",\n      \"journal\": \"Molecular omics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, single chemoproteomic method; enrichment is consistent with complex III membership but does not establish direct binding to QCR7 specifically vs. indirect co-enrichment\",\n      \"pmids\": [\"39262389\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"QCR7 (PF3D7_1012300) co-migrates with cytochrome bc1 complex (Complex III) subunits at an apparent molecular mass of ~730 kDa by complexome profiling, establishing its membership in the P. falciparum CIII dimer that also includes CYTB, CYTC1, the Rieske subunit, QCR9, QCR8, MPPα, MPPβ, and novel Apicomplexa-specific subunits C3AP1–3.\",\n      \"method\": \"Complexome profiling (blue-native PAGE fractionation coupled to quantitative mass spectrometry) across asexual blood stages and gametocytes\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — complexome profiling with quantitative MS across two life stages; co-migration across multiple fractions provides robust evidence of complex membership\",\n      \"pmids\": [\"34155201\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"QCR7 (PF3D7_1012300) is stabilised by atovaquone treatment in P. falciparum lysates as detected by solvent proteome profiling (SPP), confirming its physical association within mitochondrial Complex III that is the target of atovaquone.\",\n      \"method\": \"Solvent-induced proteome profiling (SPP) — differential protein stability analysis by mass spectrometry comparing atovaquone vs. DMSO conditions\",\n      \"journal\": \"International journal for parasitology. Drugs and drug resistance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, single proteomics-based method; stabilisation is consistent with complex membership but does not pinpoint a direct drug-binding role for QCR7\",\n      \"pmids\": [\"41308470\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"QCR7 (PF3D7_1012300) is a subunit of the P. falciparum mitochondrial cytochrome bc1 complex (Complex III), co-migrating with CYTB, CYTC1, the Rieske subunit, QCR8, QCR9, MPPα/β, and novel Apicomplexa-specific subunits in a ~730 kDa dimer; it is physically enriched by a photoactivatable analog of the antimalarial 9-methoxystrobilurin G and is stabilised by atovaquone treatment, consistent with its integral role in Complex III function, but no catalytic activity or direct binding mechanism has been experimentally defined for QCR7 itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"QCR7 (PF3D7_1012300) is a subunit of the P. falciparum mitochondrial cytochrome bc1 complex (Complex III), identified through its co-migration at ~730 kDa with the CIII dimer components CYTB, CYTC1, the Rieske subunit, QCR8, QCR9, MPPα/β, and Apicomplexa-specific subunits by complexome profiling [#1]. Its physical association within this complex is corroborated by chemoproteomic enrichment with a photoactivatable derivative of the antimalarial 9-methoxystrobilurin G [#0] and by atovaquone-induced stabilisation in solvent proteome profiling [#2], both consistent with membership in the drug-targeted Complex III. Beyond establishing QCR7 as a constituent of Complex III, the available corpus defines no catalytic activity, direct drug-binding role, or independent function for QCR7 itself.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Establishing which proteins constitute the P. falciparum Complex III was needed to define the parasite's respiratory chain organization; complexome profiling placed QCR7 within the CIII dimer.\",\n      \"evidence\": \"Blue-native PAGE fractionation coupled to quantitative mass spectrometry across asexual blood stages and gametocytes, showing co-migration at ~730 kDa\",\n      \"pmids\": [\n        \"34155201\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Co-migration establishes complex membership but not a specific structural or catalytic role for QCR7\",\n        \"No stoichiometry or direct interaction partner within the complex is resolved for QCR7\",\n        \"No structural model of QCR7 in the assembled complex\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether QCR7 is physically accessible to Complex III-targeting antimalarials was unknown; chemoproteomic profiling showed a 9MG-derived probe enriches QCR7.\",\n      \"evidence\": \"Chemoproteomic target profiling using a photoactivatable derivative of 9-methoxystrobilurin G (photo-crosslinking enrichment) in P. falciparum 3D7\",\n      \"pmids\": [\n        \"39262389\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single chemoproteomic method; enrichment does not distinguish direct probe binding to QCR7 from indirect co-enrichment via the complex\",\n        \"No binding site on QCR7 identified\",\n        \"No functional consequence of probe engagement demonstrated\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"3D7\"\n        }\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether QCR7 responds to atovaquone, the canonical Complex III inhibitor, was untested; solvent proteome profiling showed QCR7 is stabilised by atovaquone treatment.\",\n      \"evidence\": \"Solvent-induced proteome profiling (differential protein stability by mass spectrometry) comparing atovaquone vs. DMSO in P. falciparum lysates\",\n      \"pmids\": [\n        \"41308470\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single proteomics method; stabilisation reflects complex association rather than a direct QCR7 drug-binding role\",\n        \"Does not define whether QCR7 contributes to atovaquone sensitivity or resistance\",\n        \"No mechanistic link between stabilisation and QCR7 function\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic molecular function of QCR7 within Complex III, its direct interaction partners, and any independent contribution to electron transfer or complex assembly remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No catalytic activity or biochemical role assigned to QCR7 itself\",\n        \"No direct binding mechanism to any inhibitor established for QCR7\",\n        \"No genetic knockdown/knockout phenotype characterized for QCR7 in the corpus\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005743\",\n        \"supporting_discovery_ids\": [\n          1,\n          2\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0006122\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"Mitochondrial cytochrome bc1 complex (Complex III) ~730 kDa dimer\"\n    ],\n    \"partners\": [\n      \"CYTB\",\n      \"CYTC1\",\n      \"Rieske subunit\",\n      \"QCR8\",\n      \"QCR9\",\n      \"MPPα\",\n      \"MPPβ\",\n      \"C3AP1-3 (Apicomplexa-specific subunits)\"\n    ],\n    \"other_free_text\": [\n      \"Enriched by a photoactivatable derivative of the antimalarial 9-methoxystrobilurin G [#0]\",\n      \"Stabilised by atovaquone treatment in solvent proteome profiling [#2]\",\n      \"No catalytic activity or direct drug-binding mechanism defined for QCR7 itself in the corpus\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1012300","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"uncited_synthesis","uniprot_band":"empty","rules_fired":"R8","issue":"R8: 1/3 claims uncited (33%)"},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1012300","name":null,"product":"cytochrome b-c1 complex subunit 7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1210700","name":null,"product":"cytochrome b-c1 complex subunit 7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0812100","name":null,"product":"cytochrome b-c1 complex subunit 7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"QCR7","evaluation":null}