{"gene":"PF3D7_1406600","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2017,"finding":"Conditional inhibition of PfClpC (PF3D7_1406600) chaperone activity in P. falciparum results in growth arrest and apicoplast loss, which is rescued by addition of the essential apicoplast-derived metabolite IPP, demonstrating that ClpC is essential for maintaining apicoplast integrity.","method":"Conditional mutant (knockdown) with IPP rescue assay","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional KO with specific metabolite rescue and defined cellular phenotype (apicoplast loss), single lab but multiple orthogonal validations","pmids":["29141210"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"Using a double-conditional mutant parasite line, ClpC (PF3D7_1406600) chaperone activity was shown to be required to stabilize the mature PfClpP protease, revealing a functional chaperone–protease interaction in the apicoplast Clp complex.","method":"Double-conditional mutant parasite line (genetic epistasis/functional interaction assay)","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — double-conditional mutant with defined biochemical outcome (protease stability), single lab, two orthogonal conditional systems","pmids":["29141210"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Affinity purification screens identified ClpC (PF3D7_1406600) as part of the apicoplast Clp complex, whose composition includes PfClpP, PfClpS (substrate adaptor), and putative substrates; conditional mutants of each component confirmed functional interactions within the complex required for apicoplast biogenesis.","method":"Multiple affinity purification screens; conditional mutants of complex members","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal affinity purification plus conditional genetics with defined organelle phenotype, single lab but multiple orthogonal methods","pmids":["32482878"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"ClpC (PF3D7_1406600) was localized to the apicoplast of P. falciparum blood-stage parasites, and the data suggest the presence of a ClpCRP complex (ClpC with PfClpP and PfClpR) in the apicoplast.","method":"Expression confirmation in blood-stage parasites; size-exclusion chromatography, analytical ultracentrifugation, electron microscopy, and X-ray crystallography of complex members; localization inferred by apicoplast targeting","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — apicoplast localization and complex membership inferred from multiple biophysical methods on the complex, but direct localization of ClpC itself not fully detailed in abstract; single lab","pmids":["20887733"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"Plasmodium falciparum ClpS, which carries an apicoplast targeting peptide, was shown by analogy with plant ClpS1 to likely function in association with ClpC (PF3D7_1406600) in the apicoplast, consistent with an N-end rule substrate adaptor role for the ClpCS complex.","method":"Crystal structure of PfClpS (2.7 Å); peptide-binding assay in solution; apicoplast targeting peptide identification","journal":"Protein science","confidence":"Low","confidence_rationale":"Tier 3 / Weak — the ClpC–ClpS interaction is proposed by analogy with plant/bacterial systems; direct interaction between PfClpS and PfClpC (PF3D7_1406600) was not experimentally demonstrated in this paper","pmids":["26701219"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1406600 (ClpC) is an essential AAA+ chaperone localized to the P. falciparum apicoplast that forms a functional Clp complex with the PfClpP protease and the PfClpS substrate adaptor; ClpC chaperone activity is required both to maintain apicoplast integrity (loss of ClpC causes apicoplast loss rescued by IPP) and to stabilize mature PfClpP, placing it as the central regulatory chaperone of apicoplast proteostasis."},"narrative":{"mechanistic_narrative":"PF3D7_1406600 (ClpC) is an essential AAA+ chaperone of the Plasmodium falciparum apicoplast that serves as the central regulator of organellar proteostasis and biogenesis [PMID:29141210, PMID:32482878]. Conditional inhibition of ClpC chaperone activity causes parasite growth arrest and loss of the apicoplast, a defect rescued by the apicoplast-derived metabolite IPP, establishing that ClpC function is required to maintain apicoplast integrity [PMID:29141210]. ClpC operates as part of the apicoplast Clp complex, whose composition — resolved by affinity purification and conditional genetics of individual members — includes the PfClpP protease, the PfClpS substrate adaptor, and putative substrates [PMID:32482878]. Within this complex ClpC chaperone activity is required to stabilize the mature form of the PfClpP protease, defining a functional chaperone–protease coupling that underlies apicoplast proteostasis [PMID:29141210]. Beyond its role in maintaining the complex and stabilizing PfClpP, the specific substrates handled by ClpC and the structural basis of its engagement with PfClpS have not been directly characterized in the available corpus.","teleology":[{"year":2010,"claim":"Before its cellular role was known, it was unclear where ClpC acted and with what partners; localizing it to the apicoplast and placing it in a ClpC–PfClpP–PfClpR assembly established the organellar context for its function.","evidence":"Blood-stage expression plus size-exclusion chromatography, analytical ultracentrifugation, electron microscopy and X-ray crystallography of complex members in P. falciparum","pmids":["20887733"],"confidence":"Medium","gaps":["Direct localization of ClpC itself was inferred from apicoplast targeting rather than shown for the protein directly","Complex stoichiometry and whether ClpR is a stable partner not resolved","No functional consequence of complex membership tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"It was unknown whether ClpC engages a substrate adaptor; structural and targeting analysis of PfClpS raised an N-end rule adaptor partnership with ClpC, framing how substrates might be selected.","evidence":"Crystal structure of PfClpS (2.7 Å), solution peptide-binding assay, and apicoplast targeting peptide identification, with the ClpC association proposed by analogy to plant/bacterial ClpS systems","pmids":["26701219"],"confidence":"Low","gaps":["Direct physical interaction between PfClpS and ClpC was not experimentally demonstrated","No ClpC-dependent substrate delivery shown","Adaptor role inferred by cross-species analogy"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Whether ClpC is essential and what process it sustains was resolved by showing that inhibiting its chaperone activity arrests growth and destroys the apicoplast, with IPP rescue proving the defect is organelle-specific.","evidence":"Conditional knockdown mutant with IPP metabolite rescue in P. falciparum","pmids":["29141210"],"confidence":"High","gaps":["Mechanism by which loss of chaperone activity leads to apicoplast loss not defined","Direct ATPase/unfoldase substrates not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"The functional link between the chaperone and the protease was unknown; a double-conditional mutant showed ClpC activity is needed to stabilize mature PfClpP, establishing a chaperone–protease dependency within the complex.","evidence":"Double-conditional mutant parasite line assaying PfClpP maturation/stability in P. falciparum","pmids":["29141210"],"confidence":"High","gaps":["Whether stabilization is direct or through complex assembly not distinguished","Structural basis of the ClpC–ClpP interface not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"The full composition and functional interdependence of the apicoplast Clp complex was clarified by placing ClpC together with PfClpP, PfClpS and putative substrates, with conditional mutants of each confirming these interactions are required for apicoplast biogenesis.","evidence":"Multiple affinity purification screens plus conditional mutants of complex members in P. falciparum","pmids":["32482878"],"confidence":"High","gaps":["Identity of the natural ClpC substrates not established","Order of assembly and regulation of the complex not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific substrates unfolded and delivered by ClpC, and the direct structural/biochemical basis of its interactions with PfClpS and PfClpP, remain undefined in the available corpus.","evidence":"","pmids":[],"confidence":"High","gaps":["No endogenous ClpC substrate identified","No direct reconstitution of ClpC-driven unfolding/translocation","Direct ClpC–ClpS physical interaction not experimentally demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Apicoplast Clp complex (ClpC–PfClpP–PfClpS with putative substrates)","ClpCRP complex (ClpC with PfClpP and PfClpR)"],"partners":["PFCLPP (PROTEASE; STABILIZED BY CLPC)","PFCLPS (SUBSTRATE ADAPTOR)","PFCLPR"],"other_free_text":["Loss of ClpC chaperone activity causes apicoplast loss and growth arrest, rescued by IPP [#0]","ClpC chaperone activity required to stabilize mature PfClpP [#1]","ClpС–PfClpS interaction proposed by analogy to plant/bacterial N-end rule systems but not directly demonstrated [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"20887733","id":"PMC_20887733","title":"The Clp chaperones and proteases of the human malaria parasite Plasmodium falciparum.","date":"2010","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/20887733","citation_count":71,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfClpC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33497624","id":"PMC_33497624","title":"Structure, function, and substrates of Clp AAA+ protease systems in cyanobacteria, plastids, and apicoplasts: A comparative analysis.","date":"2021","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/33497624","citation_count":61,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11356517","id":"PMC_11356517","title":"A phylogenetic comparison of gene trees constructed from plastid, mitochondrial and genomic DNA of Plasmodium species.","date":"2001","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/11356517","citation_count":47,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ClpC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29141210","id":"PMC_29141210","title":"PfClpC Is an Essential Clp Chaperone Required for Plastid Integrity and Clp Protease Stability in Plasmodium falciparum.","date":"2017","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/29141210","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfClpC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22356874","id":"PMC_22356874","title":"The evolutionary host switches of Polychromophilus: a multi-gene phylogeny of the bat malaria genus suggests a second invasion of mammals by a haemosporidian parasite.","date":"2012","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/22356874","citation_count":38,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ClpC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20545854","id":"PMC_20545854","title":"A cyanobacterial serine protease of Plasmodium falciparum is targeted to the apicoplast and plays an important role in its growth and development.","date":"2010","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/20545854","citation_count":36,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26577930","id":"PMC_26577930","title":"Molecular characterization of misidentified Plasmodium ovale imported cases in Singapore.","date":"2015","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/26577930","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ClpC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32482878","id":"PMC_32482878","title":"Plastid biogenesis in malaria parasites requires the interactions and catalytic activity of the Clp proteolytic system.","date":"2020","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/32482878","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfClpC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17393186","id":"PMC_17393186","title":"Bayesian analysis of new and old malaria parasite DNA sequence data demonstrates the need for more phylogenetic signal to clarify the descent of Plasmodium falciparum.","date":"2007","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/17393186","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ClpC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19933837","id":"PMC_19933837","title":"Comparative gene evolution in haemosporidian (apicomplexa) parasites of birds and mammals.","date":"2009","source":"Molecular biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/19933837","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ClpC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26701219","id":"PMC_26701219","title":"Structure of a putative ClpS N-end rule adaptor protein from the malaria pathogen Plasmodium falciparum.","date":"2016","source":"Protein science : a publication of the Protein Society","url":"https://pubmed.ncbi.nlm.nih.gov/26701219","citation_count":24,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ClpC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34882737","id":"PMC_34882737","title":"Microbial proteasomes as drug targets.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/34882737","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28917450","id":"PMC_28917450","title":"A novel class of Plasmodial ClpP protease inhibitors as potential antimalarial agents.","date":"2017","source":"Bioorganic & medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28917450","citation_count":22,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9104,"output_tokens":1396,"usd":0.024126,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6356,"output_tokens":2540,"usd":0.04764,"stage2_stop_reason":"end_turn"},"total_usd":0.071766,"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\": 2017,\n      \"finding\": \"Conditional inhibition of PfClpC (PF3D7_1406600) chaperone activity in P. falciparum results in growth arrest and apicoplast loss, which is rescued by addition of the essential apicoplast-derived metabolite IPP, demonstrating that ClpC is essential for maintaining apicoplast integrity.\",\n      \"method\": \"Conditional mutant (knockdown) with IPP rescue assay\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with specific metabolite rescue and defined cellular phenotype (apicoplast loss), single lab but multiple orthogonal validations\",\n      \"pmids\": [\"29141210\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Using a double-conditional mutant parasite line, ClpC (PF3D7_1406600) chaperone activity was shown to be required to stabilize the mature PfClpP protease, revealing a functional chaperone–protease interaction in the apicoplast Clp complex.\",\n      \"method\": \"Double-conditional mutant parasite line (genetic epistasis/functional interaction assay)\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — double-conditional mutant with defined biochemical outcome (protease stability), single lab, two orthogonal conditional systems\",\n      \"pmids\": [\"29141210\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Affinity purification screens identified ClpC (PF3D7_1406600) as part of the apicoplast Clp complex, whose composition includes PfClpP, PfClpS (substrate adaptor), and putative substrates; conditional mutants of each component confirmed functional interactions within the complex required for apicoplast biogenesis.\",\n      \"method\": \"Multiple affinity purification screens; conditional mutants of complex members\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal affinity purification plus conditional genetics with defined organelle phenotype, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"32482878\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ClpC (PF3D7_1406600) was localized to the apicoplast of P. falciparum blood-stage parasites, and the data suggest the presence of a ClpCRP complex (ClpC with PfClpP and PfClpR) in the apicoplast.\",\n      \"method\": \"Expression confirmation in blood-stage parasites; size-exclusion chromatography, analytical ultracentrifugation, electron microscopy, and X-ray crystallography of complex members; localization inferred by apicoplast targeting\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — apicoplast localization and complex membership inferred from multiple biophysical methods on the complex, but direct localization of ClpC itself not fully detailed in abstract; single lab\",\n      \"pmids\": [\"20887733\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Plasmodium falciparum ClpS, which carries an apicoplast targeting peptide, was shown by analogy with plant ClpS1 to likely function in association with ClpC (PF3D7_1406600) in the apicoplast, consistent with an N-end rule substrate adaptor role for the ClpCS complex.\",\n      \"method\": \"Crystal structure of PfClpS (2.7 Å); peptide-binding assay in solution; apicoplast targeting peptide identification\",\n      \"journal\": \"Protein science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — the ClpC–ClpS interaction is proposed by analogy with plant/bacterial systems; direct interaction between PfClpS and PfClpC (PF3D7_1406600) was not experimentally demonstrated in this paper\",\n      \"pmids\": [\"26701219\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1406600 (ClpC) is an essential AAA+ chaperone localized to the P. falciparum apicoplast that forms a functional Clp complex with the PfClpP protease and the PfClpS substrate adaptor; ClpC chaperone activity is required both to maintain apicoplast integrity (loss of ClpC causes apicoplast loss rescued by IPP) and to stabilize mature PfClpP, placing it as the central regulatory chaperone of apicoplast proteostasis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1406600 (ClpC) is an essential AAA+ chaperone of the Plasmodium falciparum apicoplast that serves as the central regulator of organellar proteostasis and biogenesis [#0, #2]. Conditional inhibition of ClpC chaperone activity causes parasite growth arrest and loss of the apicoplast, a defect rescued by the apicoplast-derived metabolite IPP, establishing that ClpC function is required to maintain apicoplast integrity [#0]. ClpC operates as part of the apicoplast Clp complex, whose composition — resolved by affinity purification and conditional genetics of individual members — includes the PfClpP protease, the PfClpS substrate adaptor, and putative substrates [#2]. Within this complex ClpC chaperone activity is required to stabilize the mature form of the PfClpP protease, defining a functional chaperone–protease coupling that underlies apicoplast proteostasis [#1]. Beyond its role in maintaining the complex and stabilizing PfClpP, the specific substrates handled by ClpC and the structural basis of its engagement with PfClpS have not been directly characterized in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Before its cellular role was known, it was unclear where ClpC acted and with what partners; localizing it to the apicoplast and placing it in a ClpC–PfClpP–PfClpR assembly established the organellar context for its function.\",\n      \"evidence\": \"Blood-stage expression plus size-exclusion chromatography, analytical ultracentrifugation, electron microscopy and X-ray crystallography of complex members in P. falciparum\",\n      \"pmids\": [\"20887733\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct localization of ClpC itself was inferred from apicoplast targeting rather than shown for the protein directly\", \"Complex stoichiometry and whether ClpR is a stable partner not resolved\", \"No functional consequence of complex membership tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"It was unknown whether ClpC engages a substrate adaptor; structural and targeting analysis of PfClpS raised an N-end rule adaptor partnership with ClpC, framing how substrates might be selected.\",\n      \"evidence\": \"Crystal structure of PfClpS (2.7 Å), solution peptide-binding assay, and apicoplast targeting peptide identification, with the ClpC association proposed by analogy to plant/bacterial ClpS systems\",\n      \"pmids\": [\"26701219\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Direct physical interaction between PfClpS and ClpC was not experimentally demonstrated\", \"No ClpC-dependent substrate delivery shown\", \"Adaptor role inferred by cross-species analogy\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether ClpC is essential and what process it sustains was resolved by showing that inhibiting its chaperone activity arrests growth and destroys the apicoplast, with IPP rescue proving the defect is organelle-specific.\",\n      \"evidence\": \"Conditional knockdown mutant with IPP metabolite rescue in P. falciparum\",\n      \"pmids\": [\"29141210\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which loss of chaperone activity leads to apicoplast loss not defined\", \"Direct ATPase/unfoldase substrates not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The functional link between the chaperone and the protease was unknown; a double-conditional mutant showed ClpC activity is needed to stabilize mature PfClpP, establishing a chaperone–protease dependency within the complex.\",\n      \"evidence\": \"Double-conditional mutant parasite line assaying PfClpP maturation/stability in P. falciparum\",\n      \"pmids\": [\"29141210\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether stabilization is direct or through complex assembly not distinguished\", \"Structural basis of the ClpC–ClpP interface not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The full composition and functional interdependence of the apicoplast Clp complex was clarified by placing ClpC together with PfClpP, PfClpS and putative substrates, with conditional mutants of each confirming these interactions are required for apicoplast biogenesis.\",\n      \"evidence\": \"Multiple affinity purification screens plus conditional mutants of complex members in P. falciparum\",\n      \"pmids\": [\"32482878\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the natural ClpC substrates not established\", \"Order of assembly and regulation of the complex not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific substrates unfolded and delivered by ClpC, and the direct structural/biochemical basis of its interactions with PfClpS and PfClpP, remain undefined in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No endogenous ClpC substrate identified\", \"No direct reconstitution of ClpC-driven unfolding/translocation\", \"Direct ClpC–ClpS physical interaction not experimentally demonstrated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0051082\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0043335\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0010027\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\n      \"Apicoplast Clp complex (ClpC–PfClpP–PfClpS with putative substrates)\",\n      \"ClpCRP complex (ClpC with PfClpP and PfClpR)\"\n    ],\n    \"partners\": [\n      \"PfClpP (protease; stabilized by ClpC)\",\n      \"PfClpS (substrate adaptor)\",\n      \"PfClpR\"\n    ],\n    \"other_free_text\": [\n      \"Loss of ClpC chaperone activity causes apicoplast loss and growth arrest, rescued by IPP [#0]\",\n      \"ClpC chaperone activity required to stabilize mature PfClpP [#1]\",\n      \"ClpС–PfClpS interaction proposed by analogy to plant/bacterial N-end rule systems but not directly demonstrated [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1406600","name":null,"product":"ATP-dependent Clp protease regulatory subunit ClpC","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1035600","name":null,"product":"ATP-dependent Clp protease regulatory subunit ClpC, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1351500","name":null,"product":"ATP-dependent Clp protease regulatory subunit ClpC, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ClpC","evaluation":null}