{"gene":"PF3D7_1436300","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2009,"finding":"PTEX150 was identified as a novel core component of the Plasmodium translocon of exported proteins (PTEX) complex, which resides in the parasitophorous vacuole membrane and is ATP-powered, mediating protein export from the parasite into the host erythrocyte.","method":"Co-immunoprecipitation and biochemical isolation of the PTEX complex from P. falciparum","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-purification of the complex, replicated in subsequent studies, foundational discovery with multiple orthogonal methods","pmids":["19536257"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"PTEX150 is synthesized during the schizont stage and, before invasion, resides within the dense granules of invasive merozoites; upon invasion it is released into the host cell and resides in the parasitophorous vacuole membrane (PVM) for most of the subsequent cell cycle with little turnover. Biochemical fractionation indicated that PTEX components associate in the order EXP2–PTEX150–HSP101, with PTEX150 positioned between EXP2 (membrane-associated) and HSP101 in a stable macromolecular complex of >1230 kDa.","method":"Immunofluorescence assay, subcellular fractionation, Blue Native PAGE, co-immunoprecipitation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal biochemical methods (fractionation, BN-PAGE, Co-IP) in a single focused study","pmids":["22253438"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Repeated attempts to delete PTEX150 in Plasmodium berghei failed, indicating that PTEX150 is essential for blood-stage parasite survival, consistent with an obligatory role in protein export.","method":"Reverse genetics / attempted gene deletion in P. berghei","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — negative genetic result (failed deletion) replicated across two independent studies, consistent with essentiality","pmids":["23869529","24076174"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2013,"finding":"Repeated attempts to delete PTEX150 in Plasmodium berghei failed, providing genetic evidence that PTEX150 is essential for blood-stage development in the rodent malaria model.","method":"Attempted gene deletion / reverse genetics","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — failed deletion replicated in multiple independent attempts across two labs","pmids":["24076174"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"finding":"Conditional knockdown of PTEX150 in P. falciparum greatly reduced trafficking of all classes of exported proteins (both PEXEL-motif proteins and PEXEL-negative exported proteins) across the double-membrane barrier, including surface virulence factor PfEMP1, and strongly impaired blood-stage growth both in vitro and in vivo.","method":"Inducible knockdown (DiCre or TetR-based conditional system), export assays, in vitro/in vivo growth assays","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional knockdown with defined molecular phenotype (export block) replicated for multiple cargo classes, in vitro and in vivo, published in Nature","pmids":["25043043"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Cryo-EM structures of the endogenous PTEX core complex at near-atomic resolution showed that PTEX150 and EXP2 interdigitate to form a static, funnel-shaped pseudo-seven-fold-symmetric protein-conducting channel spanning the vacuolar membrane. PTEX150 was captured in both 'engaged' and 'resetting' translocation states, establishing its structural role as part of the channel through which cargo is threaded by HSP101.","method":"Cryo-electron microscopy (cryo-EM) of endogenous complex isolated using CRISPR-Cas9 epitope tags, near-atomic resolution structure determination","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 / Strong — near-atomic resolution cryo-EM structure of the endogenous complex with functional state assignments; rigorous single study with direct structural validation","pmids":["30150771"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Inactivation of PTEX150 (alongside HSP101) arrests protein export across the PVM, confirming PTEX150 as a core component required for the protein-conducting function of PTEX; PTEX150 is distinguished from EXP2 in that it does not contribute to the nutrient-permeable channel activity that EXP2 performs independently of HSP101.","method":"Regulated gene expression / conditional knockdown, patch-clamp electrophysiology, mutagenesis","journal":"Nature microbiology","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — conditional knockdown combined with electrophysiology and mutagenesis; distinguishes PTEX150's role from EXP2's dual function","pmids":["30150733"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"When export cargo is trapped (by inducibly stabilized DHFR domains), loop-like extensions appear at the PVM containing trapped cargo and EXP2, but not PTEX150 or HSP101, indicating that PTEX150 remains restricted to defined export zones on the PVM and does not redistribute into these loop extensions.","method":"Conditional DHFR-based cargo trapping, immunofluorescence colocalization, live imaging","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, direct localization experiment with functional context but limited mechanistic follow-up for PTEX150 specifically","pmids":["29696751"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PTEX150 was expressed during P. falciparum liver stages, and its promoter is active constitutively; however, ectopic restoration of HSP101 expression in P. berghei liver stages (driven by the ptex150 promoter) was insufficient to rescue PEXEL-protein export in early liver stages, indicating that PTEX150 promoter activity alone does not determine liver-stage export competence.","method":"Promoter-swap transgenics in P. berghei, immunofluorescence assay for PEXEL protein export","journal":"Frontiers in genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic epistasis experiment using PTEX150 promoter, single lab, limited direct mechanistic data about PTEX150 protein itself","pmids":["34956312"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"EXP2 and PTEX150 form a stable subcomplex that facilitates HSP101 docking onto the PTEX complex, placing PTEX150 as a structural scaffold bridging the pore-forming EXP2 and the ATPase HSP101 in the translocon assembly.","method":"Co-immunoprecipitation, biochemical fractionation, subcellular localization assays","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP identifying a stable EXP2-PTEX150 subcomplex, single lab, two complementary biochemical methods","pmids":["35192672"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"Conditional knockdown of PTEX150 perturbed haemoglobin digestion in the food vacuole; two major haemoglobin proteases (falcipain 2a and plasmepsin II) were found to interact with PTEX core components including PTEX150, implicating PTEX150 in trafficking these proteases to the parasite periphery/cytostome prior to food vacuole entry.","method":"Conditional knockdown of PTEX150, co-immunoprecipitation/interaction assays with haemoglobinases, transgenic reporter lines, haemoglobin digestion assays","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with defined phenotype (perturbed Hb digestion) plus co-IP identifying protease interactions, single lab","pmids":["37523385"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":" knockER-mediated ER sequestration of PTEX150 was used to deplete vacuolar PTEX150; this revealed that vacuolar PTEX150 (unlike HSP101) is not maintained in excess over what is needed for export, distinguishing PTEX150 from HSP101 in terms of translocon stoichiometry and spare capacity.","method":"knockER (DiCre-mediated inducible ER retrieval/sequestration), conditional protein depletion, export functional assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — novel genetic tool with functional readout, single lab, single study comparing PTEX150 and HSP101 spare capacity","pmids":["37552754"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"Conditional gene disruption (FlpL/FRT system) of ptex150 in P. falciparum sporozoites did not affect sporozoite development in mosquitoes or hepatocyte infectivity, but attenuated liver-stage growth in humanized mice (~40% reduction in fitness by day 6 post-infection). PEXEL-protein export beyond the PVM was blocked in ptex150-disrupted liver stages, and expression of some PEXEL proteins (LISP2, CSP) was reduced.","method":"Conditional gene excision (FlpL/FRT) in sporozoites, infection of humanized mice, immunofluorescence localization of PEXEL proteins","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional gene disruption with defined export and growth phenotypes in vivo, single lab but multiple orthogonal readouts","pmids":["38968107"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Mini-SURFIN4.1 (an exported integral membrane protein) forms a translocation intermediate complex containing core PTEX components EXP2, HSP101, and PTEX150, demonstrating that PTEX150 is part of the active translocation machinery engaged with integral membrane protein cargo.","method":"Co-immunoprecipitation of translocation intermediate complex, inducible cargo-clogging approach","journal":"Parasitology international","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, co-IP of intermediate complex; provides direct evidence of PTEX150 engagement with cargo during translocation","pmids":["33901679"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"PTEX150 protein was detected in P. falciparum liver-stage schizonts in humanized FRG mice, demonstrating that PTEX150 is expressed during the liver stage of infection.","method":"In vivo infection of liver-chimeric mice, immunofluorescence/protein detection in liver-stage parasites","journal":"The Journal of clinical investigation","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single detection by immunofluorescence in liver stages, no functional experiment performed on PTEX150 itself","pmids":["22996664"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PTEX150 (PF3D7_1436300) is a core structural component of the Plasmodium translocon of exported proteins (PTEX), where it interdigitates with the pore-forming protein EXP2 to form a static, funnel-shaped protein-conducting channel spanning the parasitophorous vacuole membrane, acts as a scaffold for docking of the AAA+ ATPase HSP101, and is essential for translocation of all classes of exported proteins (PEXEL and PEXEL-negative) across the vacuole membrane during blood stages, liver stages, and indirectly for haemoglobinase trafficking to the food vacuole."},"narrative":{"mechanistic_narrative":"PTEX150 (PF3D7_1436300) is a core structural component of the Plasmodium translocon of exported proteins (PTEX), the ATP-powered machinery embedded in the parasitophorous vacuole membrane (PVM) that drives export of parasite proteins into the host erythrocyte [PMID:19536257]. Within the complex, PTEX150 is positioned between the membrane-associated pore-former EXP2 and the AAA+ ATPase HSP101 in a stable macromolecular assembly of >1230 kDa, and it forms a stable subcomplex with EXP2 that provides the platform for HSP101 docking [PMID:22253438, PMID:35192672]. Cryo-EM of the endogenous complex shows PTEX150 and EXP2 interdigitating into a static, funnel-shaped, pseudo-seven-fold channel spanning the vacuolar membrane, with PTEX150 captured in distinct 'engaged' and 'resetting' translocation states as cargo is threaded through by HSP101 [PMID:30150771]. Functionally, PTEX150 is essential for blood-stage survival and is required to export all classes of cargo — both PEXEL-motif and PEXEL-negative proteins, including the virulence factor PfEMP1 — across the PVM, but it is distinct from EXP2 in that it does not contribute to the nutrient-permeable channel activity EXP2 performs independently of HSP101 [PMID:25043043, PMID:30150733]. Beyond blood stages, PTEX150 is expressed in liver stages and is required there for PEXEL-protein export and full liver-stage fitness [PMID:38968107], and its conditional depletion also perturbs haemoglobin digestion through interactions with the food-vacuole proteases falcipain 2a and plasmepsin II [PMID:37523385].","teleology":[{"year":2009,"claim":"Before its discovery it was unknown how parasite proteins crossed the parasitophorous vacuole membrane; identifying PTEX150 as a core component of an ATP-powered PVM translocon defined the physical machinery of protein export.","evidence":"Co-immunoprecipitation and biochemical isolation of the PTEX complex from P. falciparum","pmids":["19536257"],"confidence":"High","gaps":["Did not define PTEX150's specific role within the complex versus other subunits","No structural or stoichiometric information"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"The spatial and temporal logic of translocon assembly was unresolved; tracking PTEX150 from merozoite dense granules to the PVM and ordering the subunits established it as a stable scaffold positioned between EXP2 and HSP101.","evidence":"Immunofluorescence, subcellular fractionation, Blue Native PAGE and co-immunoprecipitation in P. falciparum","pmids":["22253438"],"confidence":"High","gaps":["Subunit ordering was biochemically inferred, not resolved structurally","Did not establish which subunit forms the conducting pore"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Whether PTEX operated outside blood stages was open; detecting PTEX150 protein in liver-stage schizonts showed the machinery is present during hepatic infection.","evidence":"In vivo infection of liver-chimeric FRG mice with immunofluorescence detection of PTEX150 in P. falciparum liver stages","pmids":["22996664"],"confidence":"Low","gaps":["Detection only, no functional test of PTEX150 in liver stages","Did not show liver-stage export depends on PTEX150"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"The necessity of PTEX150 for parasite viability was untested; repeated failed deletions in the rodent model provided genetic evidence that it is essential for blood-stage survival.","evidence":"Attempted gene deletion / reverse genetics in P. berghei (two independent studies)","pmids":["23869529","24076174"],"confidence":"Medium","gaps":["Failed deletion is negative evidence and does not itself define the essential molecular function","Did not distinguish an export role from other possible functions"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"claim":"It remained unknown whether PTEX150 is directly required for cargo export or merely structurally present; conditional knockdown showed that loss blocks translocation of both PEXEL and PEXEL-negative cargo and impairs growth, establishing it as functionally essential for export.","evidence":"Inducible conditional knockdown with export and in vitro/in vivo growth assays in P. falciparum","pmids":["25043043"],"confidence":"High","gaps":["Did not reveal the structural mechanism of translocation","Did not distinguish PTEX150's role from EXP2's channel activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"The physical architecture of the conducting channel and PTEX150's place in it were unknown; near-atomic cryo-EM showed PTEX150 interdigitates with EXP2 to build a static funnel-shaped channel and captured it in engaged and resetting translocation states.","evidence":"Cryo-EM of the endogenous complex isolated via CRISPR-Cas9 epitope tags in P. falciparum","pmids":["30150771"],"confidence":"High","gaps":["Static structure does not resolve the full dynamic threading cycle","HSP101 power-stroke coupling to PTEX150 not directly visualized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether PTEX150 shares EXP2's nutrient-channel function was unclear; combining knockdown with electrophysiology showed PTEX150 is required for protein export but not for the HSP101-independent nutrient-permeable channel, separating the two roles.","evidence":"Regulated knockdown, patch-clamp electrophysiology and mutagenesis in P. falciparum","pmids":["30150733"],"confidence":"High","gaps":["Did not define which PTEX150 residues mediate cargo conduction","Mechanism coupling PTEX150 to HSP101 ATP hydrolysis not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether translocon components redistribute during export was open; trapping cargo showed EXP2-containing loop extensions form at the PVM while PTEX150 stays restricted to defined export zones, indicating it does not follow cargo into these extensions.","evidence":"Conditional DHFR cargo trapping with immunofluorescence colocalization and live imaging in P. falciparum","pmids":["29696751"],"confidence":"Medium","gaps":["Single-lab localization observation with limited PTEX150-specific follow-up","Functional consequence of PTEX150 restriction not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Direct engagement of PTEX150 with integral-membrane cargo during translocation was unproven; isolating a mini-SURFIN4.1 intermediate complex containing PTEX150 showed it is part of the active cargo-engaged machinery.","evidence":"Co-immunoprecipitation of a cargo-clogged translocation intermediate in P. falciparum","pmids":["33901679"],"confidence":"Medium","gaps":["Single-lab intermediate capture","Did not resolve how integral-membrane cargo is extracted and threaded"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Whether PTEX150 promoter activity governs liver-stage export competence was tested; restoring HSP101 under the ptex150 promoter failed to rescue early liver-stage PEXEL export, showing PTEX150 promoter activity alone does not determine export competence.","evidence":"Promoter-swap transgenics in P. berghei with immunofluorescence of PEXEL export","pmids":["34956312"],"confidence":"Medium","gaps":["Indirect readout centered on HSP101, limited direct data on PTEX150 protein","Did not identify the determinant of liver-stage export competence"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"How HSP101 is recruited to the translocon was unresolved; identifying a stable EXP2-PTEX150 subcomplex that facilitates HSP101 docking established PTEX150 as a scaffold bridging the pore and the ATPase.","evidence":"Reciprocal co-immunoprecipitation and biochemical fractionation in P. falciparum","pmids":["35192672"],"confidence":"Medium","gaps":["Docking interface residues not mapped","Order of assembly in vivo not fully resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"The functional stoichiometry of the translocon was unknown; ER sequestration of PTEX150 revealed that vacuolar PTEX150, unlike HSP101, is not maintained in excess over export demand, distinguishing subunit spare capacity.","evidence":"knockER inducible ER sequestration with export functional assays in P. falciparum","pmids":["37552754"],"confidence":"Medium","gaps":["Single novel-tool study","Quantitative subunit ratios in the assembled channel not measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"A role for PTEX150 beyond export into the host was unexpected; knockdown perturbed haemoglobin digestion and PTEX core components interacted with falcipain 2a and plasmepsin II, implicating PTEX150 in trafficking haemoglobinases to the food vacuole.","evidence":"Conditional knockdown, co-immunoprecipitation with haemoglobinases, transgenic reporters and haemoglobin digestion assays in P. falciparum","pmids":["37523385"],"confidence":"Medium","gaps":["Whether the effect is direct trafficking or an indirect consequence of export failure not fully resolved","Route of protease delivery to the cytostome not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"The functional requirement for PTEX150 in liver stages was untested; conditional disruption in sporozoites left mosquito and hepatocyte-invasion stages intact but blocked liver-stage PEXEL export and attenuated liver-stage fitness in humanized mice.","evidence":"Conditional FlpL/FRT excision in sporozoites, infection of humanized mice, immunofluorescence of PEXEL proteins in P. falciparum","pmids":["38968107"],"confidence":"High","gaps":["Partial fitness reduction indicates export is not strictly required for all liver-stage growth","Cargo dependencies beyond LISP2 and CSP not enumerated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PTEX150's conformational cycling is mechanically coupled to HSP101 ATP hydrolysis to power cargo threading, and how it is targeted to defined PVM export zones, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No dynamic structural model of the full threading cycle","Determinants of PTEX150 restriction to export zones unknown","Interface residues for EXP2 and HSP101 not mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PTEX translocon core complex (EXP2–PTEX150–HSP101, >1230 kDa)","EXP2–PTEX150 stable subcomplex"],"partners":["EXP2","HSP101","FALCIPAIN 2A","PLASMEPSIN II","MINI-SURFIN4.1 (TRANSLOCATING CARGO)"],"other_free_text":["Synthesized in schizonts, stored in merozoite dense granules, released into the parasitophorous vacuole at invasion with little subsequent turnover [#1]","Interdigitates with EXP2 to form a static funnel-shaped pseudo-seven-fold protein-conducting channel; captured in 'engaged' and 'resetting' translocation states [#5]","Required for export of both PEXEL and PEXEL-negative cargo, including PfEMP1, but not for the HSP101-independent EXP2 nutrient channel [#4, #6]","Essential for blood-stage survival; not maintained in excess over export demand unlike HSP101 [#2, #3, #11]","Expressed and functionally required in liver stages for PEXEL-protein export and full fitness [#8, #12, #14]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"19536257","id":"PMC_19536257","title":"A newly discovered protein export machine in malaria parasites.","date":"2009","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/19536257","citation_count":381,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25043043","id":"PMC_25043043","title":"PTEX is an essential nexus for protein export in malaria parasites.","date":"2014","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/25043043","citation_count":207,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22996664","id":"PMC_22996664","title":"Complete Plasmodium falciparum liver-stage development in liver-chimeric mice.","date":"2012","source":"The Journal of clinical 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microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23869529","citation_count":72,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24076174","id":"PMC_24076174","title":"Two putative protein export regulators promote Plasmodium blood stage development in vivo.","date":"2013","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/24076174","citation_count":66,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22970262","id":"PMC_22970262","title":"An exported heat shock protein 40 associates with pathogenesis-related knobs in Plasmodium falciparum infected erythrocytes.","date":"2012","source":"PloS 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international","url":"https://pubmed.ncbi.nlm.nih.gov/33901679","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38968107","id":"PMC_38968107","title":"Flp/FRT-mediated disruption of ptex150 and exp2 in Plasmodium falciparum sporozoites inhibits liver-stage development.","date":"2024","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/38968107","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37523385","id":"PMC_37523385","title":"PTEX helps efficiently traffic haemoglobinases to the food vacuole in Plasmodium falciparum.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/37523385","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34956312","id":"PMC_34956312","title":"Absence of PEXEL-Dependent Protein Export in Plasmodium Liver Stages Cannot Be Restored by Gain of the HSP101 Protein Translocon ATPase.","date":"2021","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34956312","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42086568","id":"PMC_42086568","title":"Controlled human malaria infection in adults identify combinations of merozoite antigens associated with clinical immunity.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/42086568","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42155491","id":"PMC_42155491","title":"Assessing the effect of parasite antigen genetic diversity on performance of Plasmodium vivax serological exposure markers for malaria: a multicentre observational diagnostic accuracy study.","date":"2026","source":"The Lancet. Microbe","url":"https://pubmed.ncbi.nlm.nih.gov/42155491","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX150"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14000,"output_tokens":3901,"usd":0.050257,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10020,"output_tokens":5220,"usd":0.0903,"stage2_stop_reason":"end_turn"},"total_usd":0.140557,"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\": 2009,\n      \"finding\": \"PTEX150 was identified as a novel core component of the Plasmodium translocon of exported proteins (PTEX) complex, which resides in the parasitophorous vacuole membrane and is ATP-powered, mediating protein export from the parasite into the host erythrocyte.\",\n      \"method\": \"Co-immunoprecipitation and biochemical isolation of the PTEX complex from P. falciparum\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-purification of the complex, replicated in subsequent studies, foundational discovery with multiple orthogonal methods\",\n      \"pmids\": [\"19536257\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"PTEX150 is synthesized during the schizont stage and, before invasion, resides within the dense granules of invasive merozoites; upon invasion it is released into the host cell and resides in the parasitophorous vacuole membrane (PVM) for most of the subsequent cell cycle with little turnover. Biochemical fractionation indicated that PTEX components associate in the order EXP2–PTEX150–HSP101, with PTEX150 positioned between EXP2 (membrane-associated) and HSP101 in a stable macromolecular complex of >1230 kDa.\",\n      \"method\": \"Immunofluorescence assay, subcellular fractionation, Blue Native PAGE, co-immunoprecipitation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal biochemical methods (fractionation, BN-PAGE, Co-IP) in a single focused study\",\n      \"pmids\": [\"22253438\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Repeated attempts to delete PTEX150 in Plasmodium berghei failed, indicating that PTEX150 is essential for blood-stage parasite survival, consistent with an obligatory role in protein export.\",\n      \"method\": \"Reverse genetics / attempted gene deletion in P. berghei\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — negative genetic result (failed deletion) replicated across two independent studies, consistent with essentiality\",\n      \"pmids\": [\"23869529\", \"24076174\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Repeated attempts to delete PTEX150 in Plasmodium berghei failed, providing genetic evidence that PTEX150 is essential for blood-stage development in the rodent malaria model.\",\n      \"method\": \"Attempted gene deletion / reverse genetics\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — failed deletion replicated in multiple independent attempts across two labs\",\n      \"pmids\": [\"24076174\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Conditional knockdown of PTEX150 in P. falciparum greatly reduced trafficking of all classes of exported proteins (both PEXEL-motif proteins and PEXEL-negative exported proteins) across the double-membrane barrier, including surface virulence factor PfEMP1, and strongly impaired blood-stage growth both in vitro and in vivo.\",\n      \"method\": \"Inducible knockdown (DiCre or TetR-based conditional system), export assays, in vitro/in vivo growth assays\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional knockdown with defined molecular phenotype (export block) replicated for multiple cargo classes, in vitro and in vivo, published in Nature\",\n      \"pmids\": [\"25043043\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Cryo-EM structures of the endogenous PTEX core complex at near-atomic resolution showed that PTEX150 and EXP2 interdigitate to form a static, funnel-shaped pseudo-seven-fold-symmetric protein-conducting channel spanning the vacuolar membrane. PTEX150 was captured in both 'engaged' and 'resetting' translocation states, establishing its structural role as part of the channel through which cargo is threaded by HSP101.\",\n      \"method\": \"Cryo-electron microscopy (cryo-EM) of endogenous complex isolated using CRISPR-Cas9 epitope tags, near-atomic resolution structure determination\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — near-atomic resolution cryo-EM structure of the endogenous complex with functional state assignments; rigorous single study with direct structural validation\",\n      \"pmids\": [\"30150771\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Inactivation of PTEX150 (alongside HSP101) arrests protein export across the PVM, confirming PTEX150 as a core component required for the protein-conducting function of PTEX; PTEX150 is distinguished from EXP2 in that it does not contribute to the nutrient-permeable channel activity that EXP2 performs independently of HSP101.\",\n      \"method\": \"Regulated gene expression / conditional knockdown, patch-clamp electrophysiology, mutagenesis\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — conditional knockdown combined with electrophysiology and mutagenesis; distinguishes PTEX150's role from EXP2's dual function\",\n      \"pmids\": [\"30150733\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"When export cargo is trapped (by inducibly stabilized DHFR domains), loop-like extensions appear at the PVM containing trapped cargo and EXP2, but not PTEX150 or HSP101, indicating that PTEX150 remains restricted to defined export zones on the PVM and does not redistribute into these loop extensions.\",\n      \"method\": \"Conditional DHFR-based cargo trapping, immunofluorescence colocalization, live imaging\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, direct localization experiment with functional context but limited mechanistic follow-up for PTEX150 specifically\",\n      \"pmids\": [\"29696751\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PTEX150 was expressed during P. falciparum liver stages, and its promoter is active constitutively; however, ectopic restoration of HSP101 expression in P. berghei liver stages (driven by the ptex150 promoter) was insufficient to rescue PEXEL-protein export in early liver stages, indicating that PTEX150 promoter activity alone does not determine liver-stage export competence.\",\n      \"method\": \"Promoter-swap transgenics in P. berghei, immunofluorescence assay for PEXEL protein export\",\n      \"journal\": \"Frontiers in genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic epistasis experiment using PTEX150 promoter, single lab, limited direct mechanistic data about PTEX150 protein itself\",\n      \"pmids\": [\"34956312\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"EXP2 and PTEX150 form a stable subcomplex that facilitates HSP101 docking onto the PTEX complex, placing PTEX150 as a structural scaffold bridging the pore-forming EXP2 and the ATPase HSP101 in the translocon assembly.\",\n      \"method\": \"Co-immunoprecipitation, biochemical fractionation, subcellular localization assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP identifying a stable EXP2-PTEX150 subcomplex, single lab, two complementary biochemical methods\",\n      \"pmids\": [\"35192672\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Conditional knockdown of PTEX150 perturbed haemoglobin digestion in the food vacuole; two major haemoglobin proteases (falcipain 2a and plasmepsin II) were found to interact with PTEX core components including PTEX150, implicating PTEX150 in trafficking these proteases to the parasite periphery/cytostome prior to food vacuole entry.\",\n      \"method\": \"Conditional knockdown of PTEX150, co-immunoprecipitation/interaction assays with haemoglobinases, transgenic reporter lines, haemoglobin digestion assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with defined phenotype (perturbed Hb digestion) plus co-IP identifying protease interactions, single lab\",\n      \"pmids\": [\"37523385\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \" knockER-mediated ER sequestration of PTEX150 was used to deplete vacuolar PTEX150; this revealed that vacuolar PTEX150 (unlike HSP101) is not maintained in excess over what is needed for export, distinguishing PTEX150 from HSP101 in terms of translocon stoichiometry and spare capacity.\",\n      \"method\": \"knockER (DiCre-mediated inducible ER retrieval/sequestration), conditional protein depletion, export functional assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — novel genetic tool with functional readout, single lab, single study comparing PTEX150 and HSP101 spare capacity\",\n      \"pmids\": [\"37552754\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Conditional gene disruption (FlpL/FRT system) of ptex150 in P. falciparum sporozoites did not affect sporozoite development in mosquitoes or hepatocyte infectivity, but attenuated liver-stage growth in humanized mice (~40% reduction in fitness by day 6 post-infection). PEXEL-protein export beyond the PVM was blocked in ptex150-disrupted liver stages, and expression of some PEXEL proteins (LISP2, CSP) was reduced.\",\n      \"method\": \"Conditional gene excision (FlpL/FRT) in sporozoites, infection of humanized mice, immunofluorescence localization of PEXEL proteins\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional gene disruption with defined export and growth phenotypes in vivo, single lab but multiple orthogonal readouts\",\n      \"pmids\": [\"38968107\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Mini-SURFIN4.1 (an exported integral membrane protein) forms a translocation intermediate complex containing core PTEX components EXP2, HSP101, and PTEX150, demonstrating that PTEX150 is part of the active translocation machinery engaged with integral membrane protein cargo.\",\n      \"method\": \"Co-immunoprecipitation of translocation intermediate complex, inducible cargo-clogging approach\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, co-IP of intermediate complex; provides direct evidence of PTEX150 engagement with cargo during translocation\",\n      \"pmids\": [\"33901679\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"PTEX150 protein was detected in P. falciparum liver-stage schizonts in humanized FRG mice, demonstrating that PTEX150 is expressed during the liver stage of infection.\",\n      \"method\": \"In vivo infection of liver-chimeric mice, immunofluorescence/protein detection in liver-stage parasites\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single detection by immunofluorescence in liver stages, no functional experiment performed on PTEX150 itself\",\n      \"pmids\": [\"22996664\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PTEX150 (PF3D7_1436300) is a core structural component of the Plasmodium translocon of exported proteins (PTEX), where it interdigitates with the pore-forming protein EXP2 to form a static, funnel-shaped protein-conducting channel spanning the parasitophorous vacuole membrane, acts as a scaffold for docking of the AAA+ ATPase HSP101, and is essential for translocation of all classes of exported proteins (PEXEL and PEXEL-negative) across the vacuole membrane during blood stages, liver stages, and indirectly for haemoglobinase trafficking to the food vacuole.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PTEX150 (PF3D7_1436300) is a core structural component of the Plasmodium translocon of exported proteins (PTEX), the ATP-powered machinery embedded in the parasitophorous vacuole membrane (PVM) that drives export of parasite proteins into the host erythrocyte [#0]. Within the complex, PTEX150 is positioned between the membrane-associated pore-former EXP2 and the AAA+ ATPase HSP101 in a stable macromolecular assembly of >1230 kDa, and it forms a stable subcomplex with EXP2 that provides the platform for HSP101 docking [#1, #9]. Cryo-EM of the endogenous complex shows PTEX150 and EXP2 interdigitating into a static, funnel-shaped, pseudo-seven-fold channel spanning the vacuolar membrane, with PTEX150 captured in distinct 'engaged' and 'resetting' translocation states as cargo is threaded through by HSP101 [#5]. Functionally, PTEX150 is essential for blood-stage survival and is required to export all classes of cargo — both PEXEL-motif and PEXEL-negative proteins, including the virulence factor PfEMP1 — across the PVM, but it is distinct from EXP2 in that it does not contribute to the nutrient-permeable channel activity EXP2 performs independently of HSP101 [#4, #6]. Beyond blood stages, PTEX150 is expressed in liver stages and is required there for PEXEL-protein export and full liver-stage fitness [#12], and its conditional depletion also perturbs haemoglobin digestion through interactions with the food-vacuole proteases falcipain 2a and plasmepsin II [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Before its discovery it was unknown how parasite proteins crossed the parasitophorous vacuole membrane; identifying PTEX150 as a core component of an ATP-powered PVM translocon defined the physical machinery of protein export.\",\n      \"evidence\": \"Co-immunoprecipitation and biochemical isolation of the PTEX complex from P. falciparum\",\n      \"pmids\": [\"19536257\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define PTEX150's specific role within the complex versus other subunits\", \"No structural or stoichiometric information\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"The spatial and temporal logic of translocon assembly was unresolved; tracking PTEX150 from merozoite dense granules to the PVM and ordering the subunits established it as a stable scaffold positioned between EXP2 and HSP101.\",\n      \"evidence\": \"Immunofluorescence, subcellular fractionation, Blue Native PAGE and co-immunoprecipitation in P. falciparum\",\n      \"pmids\": [\"22253438\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Subunit ordering was biochemically inferred, not resolved structurally\", \"Did not establish which subunit forms the conducting pore\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Whether PTEX operated outside blood stages was open; detecting PTEX150 protein in liver-stage schizonts showed the machinery is present during hepatic infection.\",\n      \"evidence\": \"In vivo infection of liver-chimeric FRG mice with immunofluorescence detection of PTEX150 in P. falciparum liver stages\",\n      \"pmids\": [\"22996664\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Detection only, no functional test of PTEX150 in liver stages\", \"Did not show liver-stage export depends on PTEX150\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"The necessity of PTEX150 for parasite viability was untested; repeated failed deletions in the rodent model provided genetic evidence that it is essential for blood-stage survival.\",\n      \"evidence\": \"Attempted gene deletion / reverse genetics in P. berghei (two independent studies)\",\n      \"pmids\": [\"23869529\", \"24076174\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Failed deletion is negative evidence and does not itself define the essential molecular function\", \"Did not distinguish an export role from other possible functions\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"It remained unknown whether PTEX150 is directly required for cargo export or merely structurally present; conditional knockdown showed that loss blocks translocation of both PEXEL and PEXEL-negative cargo and impairs growth, establishing it as functionally essential for export.\",\n      \"evidence\": \"Inducible conditional knockdown with export and in vitro/in vivo growth assays in P. falciparum\",\n      \"pmids\": [\"25043043\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not reveal the structural mechanism of translocation\", \"Did not distinguish PTEX150's role from EXP2's channel activity\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The physical architecture of the conducting channel and PTEX150's place in it were unknown; near-atomic cryo-EM showed PTEX150 interdigitates with EXP2 to build a static funnel-shaped channel and captured it in engaged and resetting translocation states.\",\n      \"evidence\": \"Cryo-EM of the endogenous complex isolated via CRISPR-Cas9 epitope tags in P. falciparum\",\n      \"pmids\": [\"30150771\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Static structure does not resolve the full dynamic threading cycle\", \"HSP101 power-stroke coupling to PTEX150 not directly visualized\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether PTEX150 shares EXP2's nutrient-channel function was unclear; combining knockdown with electrophysiology showed PTEX150 is required for protein export but not for the HSP101-independent nutrient-permeable channel, separating the two roles.\",\n      \"evidence\": \"Regulated knockdown, patch-clamp electrophysiology and mutagenesis in P. falciparum\",\n      \"pmids\": [\"30150733\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define which PTEX150 residues mediate cargo conduction\", \"Mechanism coupling PTEX150 to HSP101 ATP hydrolysis not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether translocon components redistribute during export was open; trapping cargo showed EXP2-containing loop extensions form at the PVM while PTEX150 stays restricted to defined export zones, indicating it does not follow cargo into these extensions.\",\n      \"evidence\": \"Conditional DHFR cargo trapping with immunofluorescence colocalization and live imaging in P. falciparum\",\n      \"pmids\": [\"29696751\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab localization observation with limited PTEX150-specific follow-up\", \"Functional consequence of PTEX150 restriction not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Direct engagement of PTEX150 with integral-membrane cargo during translocation was unproven; isolating a mini-SURFIN4.1 intermediate complex containing PTEX150 showed it is part of the active cargo-engaged machinery.\",\n      \"evidence\": \"Co-immunoprecipitation of a cargo-clogged translocation intermediate in P. falciparum\",\n      \"pmids\": [\"33901679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab intermediate capture\", \"Did not resolve how integral-membrane cargo is extracted and threaded\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether PTEX150 promoter activity governs liver-stage export competence was tested; restoring HSP101 under the ptex150 promoter failed to rescue early liver-stage PEXEL export, showing PTEX150 promoter activity alone does not determine export competence.\",\n      \"evidence\": \"Promoter-swap transgenics in P. berghei with immunofluorescence of PEXEL export\",\n      \"pmids\": [\"34956312\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Indirect readout centered on HSP101, limited direct data on PTEX150 protein\", \"Did not identify the determinant of liver-stage export competence\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"How HSP101 is recruited to the translocon was unresolved; identifying a stable EXP2-PTEX150 subcomplex that facilitates HSP101 docking established PTEX150 as a scaffold bridging the pore and the ATPase.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation and biochemical fractionation in P. falciparum\",\n      \"pmids\": [\"35192672\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Docking interface residues not mapped\", \"Order of assembly in vivo not fully resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The functional stoichiometry of the translocon was unknown; ER sequestration of PTEX150 revealed that vacuolar PTEX150, unlike HSP101, is not maintained in excess over export demand, distinguishing subunit spare capacity.\",\n      \"evidence\": \"knockER inducible ER sequestration with export functional assays in P. falciparum\",\n      \"pmids\": [\"37552754\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single novel-tool study\", \"Quantitative subunit ratios in the assembled channel not measured\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"A role for PTEX150 beyond export into the host was unexpected; knockdown perturbed haemoglobin digestion and PTEX core components interacted with falcipain 2a and plasmepsin II, implicating PTEX150 in trafficking haemoglobinases to the food vacuole.\",\n      \"evidence\": \"Conditional knockdown, co-immunoprecipitation with haemoglobinases, transgenic reporters and haemoglobin digestion assays in P. falciparum\",\n      \"pmids\": [\"37523385\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the effect is direct trafficking or an indirect consequence of export failure not fully resolved\", \"Route of protease delivery to the cytostome not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The functional requirement for PTEX150 in liver stages was untested; conditional disruption in sporozoites left mosquito and hepatocyte-invasion stages intact but blocked liver-stage PEXEL export and attenuated liver-stage fitness in humanized mice.\",\n      \"evidence\": \"Conditional FlpL/FRT excision in sporozoites, infection of humanized mice, immunofluorescence of PEXEL proteins in P. falciparum\",\n      \"pmids\": [\"38968107\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Partial fitness reduction indicates export is not strictly required for all liver-stage growth\", \"Cargo dependencies beyond LISP2 and CSP not enumerated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PTEX150's conformational cycling is mechanically coupled to HSP101 ATP hydrolysis to power cargo threading, and how it is targeted to defined PVM export zones, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No dynamic structural model of the full threading cycle\", \"Determinants of PTEX150 restriction to export zones unknown\", \"Interface residues for EXP2 and HSP101 not mapped\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0015450\", \"supporting_discovery_ids\": [4, 6, 13]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [5, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020005\", \"supporting_discovery_ids\": [0, 1, 5, 7]},\n      {\"term_id\": \"GO:0020003\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0046740\", \"supporting_discovery_ids\": [0, 4, 6, 12]},\n      {\"term_id\": \"GO:0006508\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [\n      \"PTEX translocon core complex (EXP2\\u2013PTEX150\\u2013HSP101, >1230 kDa)\",\n      \"EXP2\\u2013PTEX150 stable subcomplex\"\n    ],\n    \"partners\": [\n      \"EXP2\",\n      \"HSP101\",\n      \"falcipain 2a\",\n      \"plasmepsin II\",\n      \"mini-SURFIN4.1 (translocating cargo)\"\n    ],\n    \"other_free_text\": [\n      \"Synthesized in schizonts, stored in merozoite dense granules, released into the parasitophorous vacuole at invasion with little subsequent turnover [#1]\",\n      \"Interdigitates with EXP2 to form a static funnel-shaped pseudo-seven-fold protein-conducting channel; captured in 'engaged' and 'resetting' translocation states [#5]\",\n      \"Required for export of both PEXEL and PEXEL-negative cargo, including PfEMP1, but not for the HSP101-independent EXP2 nutrient channel [#4, #6]\",\n      \"Essential for blood-stage survival; not maintained in excess over export demand unlike HSP101 [#2, #3, #11]\",\n      \"Expressed and functionally required in liver stages for PEXEL-protein export and full fitness [#8, #12, #14]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1436300","name":null,"product":"translocon component PTEX150","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1008500","name":null,"product":"translocon component PTEX150","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0422900","name":null,"product":"translocon component PTEX150, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"Pf112","evaluation":null}