{"gene":"PF3D7_1443400","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2015,"finding":"WLP1 (PF3D7_1443400) was identified as a WD40-repeat protein that co-immunoprecipitates with PfAMA1 in mature schizonts, and with PfCCp1 and Pfs230 in gametocytes, indicating it associates with adhesion protein complexes in both blood-stage forms.","method":"Co-immunoprecipitation followed by mass spectrometry; immunohistochemistry for localization","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP/MS interaction identification with localization data, single lab, no reciprocal pulldown reported","pmids":["26537493"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"In mature schizonts, WLP1 localizes underneath the merozoite micronemes; in gametocytes it accumulates underneath the plasma membrane, as determined by immunohistochemistry.","method":"Immunohistochemistry / immunofluorescence localization","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment, single lab, two stage-specific localizations reported","pmids":["26537493"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Attempts to disrupt the pfwlp1 gene by reverse genetics failed, while HA-tagging was feasible, suggesting WLP1 performs a crucial (essential) function during blood-stage replication.","method":"Reverse genetics (attempted gene disruption)","journal":"Malaria journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — essentiality inferred from failed disruption, single lab, single method, no conditional knockdown at this stage","pmids":["26537493"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Knockdown of WLP1 in gametocytes led to reduced protein levels of the LCCL-domain proteins PfCCp1 and PfCCp2, establishing that WLP1 is required for the stability of the PfCCp-based adhesion protein complex.","method":"Reverse genetics-based knockdown parasite line; immunoblot for PfCCp1 and PfCCp2 protein levels","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with defined molecular phenotype (reduced complex component levels), single lab, two orthogonal readouts (protein levels and functional assay)","pmids":["35923798"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"WLP1 knockdown resulted in significantly impaired gametocyte exflagellation (male gamete formation), linking WLP1's role in adhesion complex stability to a functional requirement for gametogenesis.","method":"Reverse genetics knockdown; exflagellation assay","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with defined functional phenotype (exflagellation), single lab","pmids":["35923798"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"WLP1 (PF3D7_1443400) is a WD40-repeat scaffold protein in Plasmodium falciparum that localizes beneath the merozoite micronemes in schizonts and beneath the plasma membrane in gametocytes, where it physically associates with adhesion protein complexes (PfAMA1 in merozoites; PfCCp1, PfCCp2, and Pfs230 in gametocytes) and is required for the stability of these complexes and for gametocyte exflagellation."},"narrative":{"mechanistic_narrative":"WLP1 (PF3D7_1443400) is a WD40-repeat protein of Plasmodium falciparum that functions as a scaffold associating with adhesion protein complexes in both asexual and sexual blood-stage forms [PMID:26537493]. It co-immunoprecipitates with PfAMA1 in mature schizonts and with the LCCL-domain protein PfCCp1 and the gamete surface protein Pfs230 in gametocytes, and localizes beneath the merozoite micronemes in schizonts and beneath the plasma membrane in gametocytes [PMID:26537493]. Functionally, WLP1 is required for the stability of the PfCCp-based adhesion complex: its knockdown reduces PfCCp1 and PfCCp2 protein levels and significantly impairs gametocyte exflagellation, linking complex integrity to male gametogenesis [PMID:35923798]. Beyond its role as a stabilizing partner of these adhesion complexes, no enzymatic activity or structural mechanism for WLP1 has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"Establishing what WLP1 does began with defining its physical partners, showing it is not a standalone factor but a WD40-repeat protein embedded in stage-specific adhesion protein complexes.","evidence":"Co-immunoprecipitation and mass spectrometry from schizonts and gametocytes","pmids":["26537493"],"confidence":"Medium","gaps":["No reciprocal pulldown from the partner proteins","Direct versus indirect nature of the associations within the complex unresolved","Stoichiometry and architecture of the complex unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Localizing WLP1 tested whether its position was consistent with a role at adhesion complexes, placing it beneath the micronemes in schizonts and beneath the plasma membrane in gametocytes.","evidence":"Immunohistochemistry / immunofluorescence in schizonts and gametocytes","pmids":["26537493"],"confidence":"Medium","gaps":["Submembranous localization not resolved to a specific organelle or scaffold","Whether localization depends on its partners is untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"The question of whether WLP1 is dispensable was probed by attempted gene disruption, which failed while tagging succeeded, implicating an essential blood-stage function.","evidence":"Reverse genetics attempted disruption versus successful HA-tagging","pmids":["26537493"],"confidence":"Low","gaps":["Essentiality inferred from failed disruption, not from conditional knockdown at this stage","Single method, no rescue","Specific essential step not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Conditional knockdown answered why WLP1 associates with the PfCCp complex, showing it is required to maintain the levels of complex components PfCCp1 and PfCCp2.","evidence":"Knockdown parasite line with immunoblot readout of PfCCp1/PfCCp2","pmids":["35923798"],"confidence":"Medium","gaps":["Mechanism of stabilization (assembly, trafficking, or turnover) not defined","Whether stabilization involves direct binding is unknown","Effect on the schizont PfAMA1 association not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Linking the molecular phenotype to biology, WLP1 knockdown impaired gametocyte exflagellation, tying its complex-stabilizing role to male gametogenesis.","evidence":"Reverse genetics knockdown with exflagellation assay","pmids":["35923798"],"confidence":"Medium","gaps":["Causal chain from complex destabilization to exflagellation failure not dissected","Effect on transmission to mosquito untested","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The biochemical function of the WD40 scaffold and the mechanism by which it stabilizes adhesion complexes remain unknown.","evidence":"No experiment in the corpus addresses WLP1 structure, direct binding surfaces, or its role in the schizont PfAMA1 complex.","pmids":[],"confidence":"Low","gaps":["No structural model or defined interaction interface","Direct versus indirect binding to PfAMA1, PfCCp1/2, and Pfs230 unresolved","Functional consequence of WLP1 loss for merozoite invasion not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfAMA1-associated adhesion complex (schizont)","PfCCp1/PfCCp2/Pfs230 LCCL-domain adhesion complex (gametocyte)"],"partners":["PFAMA1","PFCCP1","PFCCP2","PFS230"],"other_free_text":["WD40-repeat protein required for stability of the PfCCp-based adhesion complex [#3]","Required for gametocyte exflagellation / male gamete formation [#4]","Gene disruption attempts failed while HA-tagging succeeded, implying essential blood-stage function [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"26537493","id":"PMC_26537493","title":"A WD40-repeat protein unique to malaria parasites associates with adhesion protein complexes and is crucial for blood stage progeny.","date":"2015","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/26537493","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfWLP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35923798","id":"PMC_35923798","title":"The WD40-Protein PfWLP1 Ensures Stability of the PfCCp-Based Adhesion Protein Complex in Plasmodium falciparum Gametocytes.","date":"2022","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35923798","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfWLP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3904,"output_tokens":1212,"usd":0.014946,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6083,"output_tokens":2303,"usd":0.043995,"stage2_stop_reason":"end_turn"},"total_usd":0.058941,"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\": 2015,\n      \"finding\": \"WLP1 (PF3D7_1443400) was identified as a WD40-repeat protein that co-immunoprecipitates with PfAMA1 in mature schizonts, and with PfCCp1 and Pfs230 in gametocytes, indicating it associates with adhesion protein complexes in both blood-stage forms.\",\n      \"method\": \"Co-immunoprecipitation followed by mass spectrometry; immunohistochemistry for localization\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP/MS interaction identification with localization data, single lab, no reciprocal pulldown reported\",\n      \"pmids\": [\"26537493\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In mature schizonts, WLP1 localizes underneath the merozoite micronemes; in gametocytes it accumulates underneath the plasma membrane, as determined by immunohistochemistry.\",\n      \"method\": \"Immunohistochemistry / immunofluorescence localization\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment, single lab, two stage-specific localizations reported\",\n      \"pmids\": [\"26537493\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Attempts to disrupt the pfwlp1 gene by reverse genetics failed, while HA-tagging was feasible, suggesting WLP1 performs a crucial (essential) function during blood-stage replication.\",\n      \"method\": \"Reverse genetics (attempted gene disruption)\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — essentiality inferred from failed disruption, single lab, single method, no conditional knockdown at this stage\",\n      \"pmids\": [\"26537493\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Knockdown of WLP1 in gametocytes led to reduced protein levels of the LCCL-domain proteins PfCCp1 and PfCCp2, establishing that WLP1 is required for the stability of the PfCCp-based adhesion protein complex.\",\n      \"method\": \"Reverse genetics-based knockdown parasite line; immunoblot for PfCCp1 and PfCCp2 protein levels\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with defined molecular phenotype (reduced complex component levels), single lab, two orthogonal readouts (protein levels and functional assay)\",\n      \"pmids\": [\"35923798\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"WLP1 knockdown resulted in significantly impaired gametocyte exflagellation (male gamete formation), linking WLP1's role in adhesion complex stability to a functional requirement for gametogenesis.\",\n      \"method\": \"Reverse genetics knockdown; exflagellation assay\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with defined functional phenotype (exflagellation), single lab\",\n      \"pmids\": [\"35923798\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"WLP1 (PF3D7_1443400) is a WD40-repeat scaffold protein in Plasmodium falciparum that localizes beneath the merozoite micronemes in schizonts and beneath the plasma membrane in gametocytes, where it physically associates with adhesion protein complexes (PfAMA1 in merozoites; PfCCp1, PfCCp2, and Pfs230 in gametocytes) and is required for the stability of these complexes and for gametocyte exflagellation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"WLP1 (PF3D7_1443400) is a WD40-repeat protein of Plasmodium falciparum that functions as a scaffold associating with adhesion protein complexes in both asexual and sexual blood-stage forms [#0]. It co-immunoprecipitates with PfAMA1 in mature schizonts and with the LCCL-domain protein PfCCp1 and the gamete surface protein Pfs230 in gametocytes, and localizes beneath the merozoite micronemes in schizonts and beneath the plasma membrane in gametocytes [#0, #1]. Functionally, WLP1 is required for the stability of the PfCCp-based adhesion complex: its knockdown reduces PfCCp1 and PfCCp2 protein levels and significantly impairs gametocyte exflagellation, linking complex integrity to male gametogenesis [#3, #4]. Beyond its role as a stabilizing partner of these adhesion complexes, no enzymatic activity or structural mechanism for WLP1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Establishing what WLP1 does began with defining its physical partners, showing it is not a standalone factor but a WD40-repeat protein embedded in stage-specific adhesion protein complexes.\",\n      \"evidence\": \"Co-immunoprecipitation and mass spectrometry from schizonts and gametocytes\",\n      \"pmids\": [\"26537493\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reciprocal pulldown from the partner proteins\", \"Direct versus indirect nature of the associations within the complex unresolved\", \"Stoichiometry and architecture of the complex unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Localizing WLP1 tested whether its position was consistent with a role at adhesion complexes, placing it beneath the micronemes in schizonts and beneath the plasma membrane in gametocytes.\",\n      \"evidence\": \"Immunohistochemistry / immunofluorescence in schizonts and gametocytes\",\n      \"pmids\": [\"26537493\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Submembranous localization not resolved to a specific organelle or scaffold\", \"Whether localization depends on its partners is untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"The question of whether WLP1 is dispensable was probed by attempted gene disruption, which failed while tagging succeeded, implicating an essential blood-stage function.\",\n      \"evidence\": \"Reverse genetics attempted disruption versus successful HA-tagging\",\n      \"pmids\": [\"26537493\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Essentiality inferred from failed disruption, not from conditional knockdown at this stage\", \"Single method, no rescue\", \"Specific essential step not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Conditional knockdown answered why WLP1 associates with the PfCCp complex, showing it is required to maintain the levels of complex components PfCCp1 and PfCCp2.\",\n      \"evidence\": \"Knockdown parasite line with immunoblot readout of PfCCp1/PfCCp2\",\n      \"pmids\": [\"35923798\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of stabilization (assembly, trafficking, or turnover) not defined\", \"Whether stabilization involves direct binding is unknown\", \"Effect on the schizont PfAMA1 association not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linking the molecular phenotype to biology, WLP1 knockdown impaired gametocyte exflagellation, tying its complex-stabilizing role to male gametogenesis.\",\n      \"evidence\": \"Reverse genetics knockdown with exflagellation assay\",\n      \"pmids\": [\"35923798\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal chain from complex destabilization to exflagellation failure not dissected\", \"Effect on transmission to mosquito untested\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical function of the WD40 scaffold and the mechanism by which it stabilizes adhesion complexes remain unknown.\",\n      \"evidence\": \"No experiment in the corpus addresses WLP1 structure, direct binding surfaces, or its role in the schizont PfAMA1 complex.\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model or defined interaction interface\", \"Direct versus indirect binding to PfAMA1, PfCCp1/2, and Pfs230 unresolved\", \"Functional consequence of WLP1 loss for merozoite invasion not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0030674\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007140\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"PfAMA1-associated adhesion complex (schizont)\",\n      \"PfCCp1/PfCCp2/Pfs230 LCCL-domain adhesion complex (gametocyte)\"\n    ],\n    \"partners\": [\n      \"PfAMA1\",\n      \"PfCCp1\",\n      \"PfCCp2\",\n      \"Pfs230\"\n    ],\n    \"other_free_text\": [\n      \"WD40-repeat protein required for stability of the PfCCp-based adhesion complex [#3]\",\n      \"Required for gametocyte exflagellation / male gamete formation [#4]\",\n      \"Gene disruption attempts failed while HA-tagging succeeded, implying essential blood-stage function [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1443400","name":null,"product":"WD repeat-containing protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1307300","name":null,"product":"WD repeat-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1238900","name":null,"product":"WD repeat-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"WLP1","evaluation":null}