{"gene":"PF3D7_0404900","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2005,"finding":"P41 (PF3D7_0404900) was identified as a GPI-anchored merozoite surface antigen enriched in detergent-resistant membranes (lipid rafts) of P. falciparum, possessing six-cysteine (Cys6) motifs and recognized by antibodies from naturally infected individuals.","method":"Proteomics of gradient-purified detergent-resistant membranes; antibody recognition validated by immunological assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical fractionation and proteomic identification with immunological validation, single lab","pmids":["16203726"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"Native P41 and P12 form a stable heterodimer on the infective merozoite surface in P. falciparum, and the complex is secreted following erythrocyte invasion. Genetic disruption of P41 in P. falciparum produced no detectable growth defect in vitro and no obvious phenotypic changes, indicating P41 is dispensable for blood-stage replication under standard culture conditions.","method":"Co-immunoprecipitation of native proteins; gene knockout by homologous recombination with in vitro growth assays","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal native Co-IP confirming heterodimer, independent KO with phenotypic readout, replicated in subsequent studies","pmids":["22848665"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Recombinant full-length ectodomains of P12 and P41 directly interact in a biochemically active form when expressed in a mammalian system, confirming the P12-P41 heterodimeric complex.","method":"Mammalian expression of recombinant ectodomains; direct protein-protein interaction assay (AVEXIS or equivalent low-affinity detection method)","journal":"Molecular & cellular proteomics : MCP","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — recombinant protein interaction assay, single lab, corroborates native Co-IP from a separate study","pmids":["24043421"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Chemical cross-linking and mass spectrometry confirmed the Pf12-P41 heterodimeric complex and supported an antiparallel orientation of the two proteins, with P41 interacting with Pf12 via specific inter-domain cross-links.","method":"Chemical cross-linking coupled to mass spectrometry; crystal structure of Pf12 alone used to interpret cross-link geometry","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — cross-linking MS provides structural constraints on the complex, single lab, corroborated by crystal structure of binding partner","pmids":["23511632"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Recombinant P. vivax P12 and P41 orthologs interact with each other, confirming conservation of the P12-P41 heterodimeric interaction across Plasmodium species.","method":"AVEXIS (low-affinity extracellular protein-protein interaction detection assay) using recombinant mammalian-expressed ectodomains; confirmed by surface plasmon resonance for other interactions in the same study","journal":"PLoS neglected tropical diseases","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — AVEXIS assay with recombinant proteins, single lab, orthologous finding consistent with P. falciparum data","pmids":["26701602"],"is_preprint":false,"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2011,"finding":"Targeted gene deletion of the P. berghei ortholog of P41 confirmed it is non-essential for asexual blood-stage development in vivo.","method":"piggyBac transposon-mediated insertion and targeted gene deletion; phenotypic assessment in P. berghei blood-stage growth","journal":"BMC genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — targeted gene deletion with in vivo phenotypic readout, single lab, consistent with P. falciparum KO data","pmids":["21418605"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"Crystal structure of the Pf12-P41 heterodimeric complex was solved at 2.85 Å resolution, revealing two critical interfaces required for complex formation. Structure-function analyses identified key residues at the interface, and nanobodies targeting Pf12 were shown to sterically block Pf12-P41 complex formation.","method":"X-ray crystallography at 2.85 Å; site-directed mutagenesis of interface residues; nanobody generation and crystal structure of nanobody-Pf12 complex; complex formation inhibition assay","journal":"FEMS microbes","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with mutagenesis validation and functional inhibition by nanobodies, multiple orthogonal methods in one study","pmids":["35308105"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"P41 and P12 do not appear to function as adhesins mediating erythrocyte-receptor binding, as the recombinant P12-P41 complex showed no evidence of erythrocyte-receptor binding, and antisera to these proteins did not substantially inhibit erythrocyte invasion (negative result).","method":"Recombinant protein erythrocyte binding assay; erythrocyte invasion inhibition assay with antisera","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct erythrocyte binding assay and invasion inhibition assay, single lab, negative result with clear experimental controls","pmids":["22848665"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P41 (PF3D7_0404900) is a GPI-anchored six-cysteine family protein present on the P. falciparum merozoite surface within lipid rafts, where it forms a stable heterodimer with P12 via two defined structural interfaces (resolved by X-ray crystallography at 2.85 Å); the complex is secreted after erythrocyte invasion, does not mediate erythrocyte-receptor binding, and is dispensable for asexual blood-stage replication in both P. falciparum and P. berghei knockouts, suggesting a redundant or immune-evasion role rather than an essential invasion adhesin function."},"narrative":{"mechanistic_narrative":"P41 (PF3D7_0404900) is a GPI-anchored six-cysteine (Cys6) family surface antigen of the Plasmodium falciparum merozoite, enriched in detergent-resistant membrane microdomains (lipid rafts) and recognized by antibodies from naturally infected individuals [PMID:16203726]. Its defining molecular activity is the formation of a stable heterodimer with P12: native P41 and P12 co-immunoprecipitate on the infective merozoite surface, and the complex is secreted following erythrocyte invasion [PMID:22848665], an interaction independently reconstituted with recombinant ectodomains [PMID:24043421] and conserved in the P. vivax orthologs [PMID:26701602]. Structural work resolved the Pf12-P41 heterodimer by X-ray crystallography at 2.85 Å, defining two critical interfaces required for complex formation whose key residues were validated by mutagenesis and whose assembly can be sterically blocked by anti-Pf12 nanobodies [PMID:35308105]; cross-linking mass spectrometry earlier supported an antiparallel arrangement of the two subunits [PMID:23511632]. P41 does not function as an invasion adhesin: the recombinant P12-P41 complex shows no erythrocyte-receptor binding and antisera do not substantially inhibit invasion [PMID:22848665], and targeted disruption of P41 causes no growth defect during asexual blood-stage replication in P. falciparum [PMID:22848665] or of its ortholog in P. berghei [PMID:21418605], indicating a dispensable, potentially redundant or immune-evasion role. Beyond its heterodimeric partnership with P12 and surface/raft localization, no downstream effector function of P41 has been characterized in the available corpus.","teleology":[{"year":2005,"claim":"Establishing where P41 resides and how the host sees it was the first step: it was identified as a GPI-anchored, raft-associated merozoite surface antigen bearing six-cysteine motifs and recognized by immune sera.","evidence":"Proteomics of detergent-resistant membranes with immunological antibody validation in P. falciparum","pmids":["16203726"],"confidence":"Medium","gaps":["No binding partner or function assigned at this stage","Raft association not linked to a molecular activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Whether P41 is required for parasite propagation was tested by deleting the P. berghei ortholog, which showed asexual blood-stage development proceeds normally without it.","evidence":"Targeted gene deletion / piggyBac insertion with in vivo blood-stage phenotyping in P. berghei","pmids":["21418605"],"confidence":"Medium","gaps":["Non-essentiality could reflect redundancy not tested","Other life-cycle stages not assessed"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2012,"claim":"The central question of P41's molecular role was addressed by showing it forms a native heterodimer with P12 that is secreted after invasion, is dispensable for blood-stage growth, and is not an erythrocyte-binding adhesin.","evidence":"Native reciprocal Co-IP, gene knockout with in vitro growth assays, and erythrocyte binding/invasion-inhibition assays in P. falciparum","pmids":["22848665"],"confidence":"High","gaps":["Functional role of the secreted complex not defined","Redundancy with sibling Cys6 proteins untested","Negative invasion result does not exclude a role in other host interactions"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"The heterodimer was confirmed biochemically and given a coarse architecture: recombinant ectodomains interact directly, and cross-linking MS placed the two proteins in an antiparallel orientation.","evidence":"Recombinant mammalian-expressed ectodomain interaction assay and chemical cross-linking coupled to mass spectrometry in P. falciparum","pmids":["24043421","23511632"],"confidence":"Medium","gaps":["Cross-linking geometry interpreted with a partner-only crystal structure","Interface residues not yet defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Evolutionary conservation of the interaction was established by showing the P. vivax P12 and P41 orthologs also heterodimerize.","evidence":"AVEXIS interaction assay with recombinant ectodomains in P. vivax","pmids":["26701602"],"confidence":"Medium","gaps":["Conservation of function, not just binding, remains unaddressed","In vivo relevance in P. vivax untested"],"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2022,"claim":"The high-resolution architecture and druggability of the complex were resolved, defining two interfaces required for assembly and demonstrating that assembly can be blocked pharmacologically.","evidence":"X-ray crystallography of the Pf12-P41 complex at 2.85 Å, interface mutagenesis, and nanobody-mediated inhibition of complex formation in P. falciparum","pmids":["35308105"],"confidence":"High","gaps":["Biological consequence of blocking the complex not demonstrated","No downstream effector or ligand identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The biological function of the P12-P41 complex remains unknown: it is surface-localized, secreted after invasion, and non-adhesive, but no effector activity, ligand, or phenotype tied to its loss has been identified.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No demonstrated function for the secreted complex","Proposed immune-evasion or redundant role untested","No genetic redundancy experiment with sibling Cys6 proteins"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Pf12-P41 heterodimer"],"partners":["P12 (PF12)"],"other_free_text":["GPI-anchored six-cysteine (Cys6) family merozoite surface antigen [#0]","Recognized by antibodies from naturally infected individuals [#0]","Complex secreted following erythrocyte invasion [#1]","Dispensable for asexual blood-stage replication in P. falciparum [#1] and P. berghei [#5]","Not an erythrocyte-receptor-binding adhesin; antisera do not substantially inhibit invasion [#7]","P12-P41 interaction conserved in P. vivax orthologs [#4]","Two interfaces required for complex formation; assembly blockable by anti-Pf12 nanobodies [#6]","Antiparallel subunit orientation inferred from cross-linking MS [#3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16203726","id":"PMC_16203726","title":"Distinct protein classes including novel merozoite surface antigens in Raft-like membranes of Plasmodium falciparum.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16203726","citation_count":187,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20386715","id":"PMC_20386715","title":"Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility.","date":"2010","source":"PLoS 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antibodies from naturally infected individuals.\",\n      \"method\": \"Proteomics of gradient-purified detergent-resistant membranes; antibody recognition validated by immunological assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical fractionation and proteomic identification with immunological validation, single lab\",\n      \"pmids\": [\"16203726\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Native P41 and P12 form a stable heterodimer on the infective merozoite surface in P. falciparum, and the complex is secreted following erythrocyte invasion. Genetic disruption of P41 in P. falciparum produced no detectable growth defect in vitro and no obvious phenotypic changes, indicating P41 is dispensable for blood-stage replication under standard culture conditions.\",\n      \"method\": \"Co-immunoprecipitation of native proteins; gene knockout by homologous recombination with in vitro growth assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal native Co-IP confirming heterodimer, independent KO with phenotypic readout, replicated in subsequent studies\",\n      \"pmids\": [\"22848665\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Recombinant full-length ectodomains of P12 and P41 directly interact in a biochemically active form when expressed in a mammalian system, confirming the P12-P41 heterodimeric complex.\",\n      \"method\": \"Mammalian expression of recombinant ectodomains; direct protein-protein interaction assay (AVEXIS or equivalent low-affinity detection method)\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — recombinant protein interaction assay, single lab, corroborates native Co-IP from a separate study\",\n      \"pmids\": [\"24043421\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Chemical cross-linking and mass spectrometry confirmed the Pf12-P41 heterodimeric complex and supported an antiparallel orientation of the two proteins, with P41 interacting with Pf12 via specific inter-domain cross-links.\",\n      \"method\": \"Chemical cross-linking coupled to mass spectrometry; crystal structure of Pf12 alone used to interpret cross-link geometry\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — cross-linking MS provides structural constraints on the complex, single lab, corroborated by crystal structure of binding partner\",\n      \"pmids\": [\"23511632\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Recombinant P. vivax P12 and P41 orthologs interact with each other, confirming conservation of the P12-P41 heterodimeric interaction across Plasmodium species.\",\n      \"method\": \"AVEXIS (low-affinity extracellular protein-protein interaction detection assay) using recombinant mammalian-expressed ectodomains; confirmed by surface plasmon resonance for other interactions in the same study\",\n      \"journal\": \"PLoS neglected tropical diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — AVEXIS assay with recombinant proteins, single lab, orthologous finding consistent with P. falciparum data\",\n      \"pmids\": [\"26701602\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Targeted gene deletion of the P. berghei ortholog of P41 confirmed it is non-essential for asexual blood-stage development in vivo.\",\n      \"method\": \"piggyBac transposon-mediated insertion and targeted gene deletion; phenotypic assessment in P. berghei blood-stage growth\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — targeted gene deletion with in vivo phenotypic readout, single lab, consistent with P. falciparum KO data\",\n      \"pmids\": [\"21418605\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Crystal structure of the Pf12-P41 heterodimeric complex was solved at 2.85 Å resolution, revealing two critical interfaces required for complex formation. Structure-function analyses identified key residues at the interface, and nanobodies targeting Pf12 were shown to sterically block Pf12-P41 complex formation.\",\n      \"method\": \"X-ray crystallography at 2.85 Å; site-directed mutagenesis of interface residues; nanobody generation and crystal structure of nanobody-Pf12 complex; complex formation inhibition assay\",\n      \"journal\": \"FEMS microbes\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with mutagenesis validation and functional inhibition by nanobodies, multiple orthogonal methods in one study\",\n      \"pmids\": [\"35308105\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"P41 and P12 do not appear to function as adhesins mediating erythrocyte-receptor binding, as the recombinant P12-P41 complex showed no evidence of erythrocyte-receptor binding, and antisera to these proteins did not substantially inhibit erythrocyte invasion (negative result).\",\n      \"method\": \"Recombinant protein erythrocyte binding assay; erythrocyte invasion inhibition assay with antisera\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct erythrocyte binding assay and invasion inhibition assay, single lab, negative result with clear experimental controls\",\n      \"pmids\": [\"22848665\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P41 (PF3D7_0404900) is a GPI-anchored six-cysteine family protein present on the P. falciparum merozoite surface within lipid rafts, where it forms a stable heterodimer with P12 via two defined structural interfaces (resolved by X-ray crystallography at 2.85 Å); the complex is secreted after erythrocyte invasion, does not mediate erythrocyte-receptor binding, and is dispensable for asexual blood-stage replication in both P. falciparum and P. berghei knockouts, suggesting a redundant or immune-evasion role rather than an essential invasion adhesin function.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"P41 (PF3D7_0404900) is a GPI-anchored six-cysteine (Cys6) family surface antigen of the Plasmodium falciparum merozoite, enriched in detergent-resistant membrane microdomains (lipid rafts) and recognized by antibodies from naturally infected individuals [#0]. Its defining molecular activity is the formation of a stable heterodimer with P12: native P41 and P12 co-immunoprecipitate on the infective merozoite surface, and the complex is secreted following erythrocyte invasion [#1], an interaction independently reconstituted with recombinant ectodomains [#2] and conserved in the P. vivax orthologs [#4]. Structural work resolved the Pf12-P41 heterodimer by X-ray crystallography at 2.85 Å, defining two critical interfaces required for complex formation whose key residues were validated by mutagenesis and whose assembly can be sterically blocked by anti-Pf12 nanobodies [#6]; cross-linking mass spectrometry earlier supported an antiparallel arrangement of the two subunits [#3]. P41 does not function as an invasion adhesin: the recombinant P12-P41 complex shows no erythrocyte-receptor binding and antisera do not substantially inhibit invasion [#7], and targeted disruption of P41 causes no growth defect during asexual blood-stage replication in P. falciparum [#1] or of its ortholog in P. berghei [#5], indicating a dispensable, potentially redundant or immune-evasion role. Beyond its heterodimeric partnership with P12 and surface/raft localization, no downstream effector function of P41 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing where P41 resides and how the host sees it was the first step: it was identified as a GPI-anchored, raft-associated merozoite surface antigen bearing six-cysteine motifs and recognized by immune sera.\",\n      \"evidence\": \"Proteomics of detergent-resistant membranes with immunological antibody validation in P. falciparum\",\n      \"pmids\": [\"16203726\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No binding partner or function assigned at this stage\", \"Raft association not linked to a molecular activity\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Whether P41 is required for parasite propagation was tested by deleting the P. berghei ortholog, which showed asexual blood-stage development proceeds normally without it.\",\n      \"evidence\": \"Targeted gene deletion / piggyBac insertion with in vivo blood-stage phenotyping in P. berghei\",\n      \"pmids\": [\"21418605\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Non-essentiality could reflect redundancy not tested\", \"Other life-cycle stages not assessed\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"The central question of P41's molecular role was addressed by showing it forms a native heterodimer with P12 that is secreted after invasion, is dispensable for blood-stage growth, and is not an erythrocyte-binding adhesin.\",\n      \"evidence\": \"Native reciprocal Co-IP, gene knockout with in vitro growth assays, and erythrocyte binding/invasion-inhibition assays in P. falciparum\",\n      \"pmids\": [\"22848665\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional role of the secreted complex not defined\", \"Redundancy with sibling Cys6 proteins untested\", \"Negative invasion result does not exclude a role in other host interactions\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"The heterodimer was confirmed biochemically and given a coarse architecture: recombinant ectodomains interact directly, and cross-linking MS placed the two proteins in an antiparallel orientation.\",\n      \"evidence\": \"Recombinant mammalian-expressed ectodomain interaction assay and chemical cross-linking coupled to mass spectrometry in P. falciparum\",\n      \"pmids\": [\"24043421\", \"23511632\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cross-linking geometry interpreted with a partner-only crystal structure\", \"Interface residues not yet defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Evolutionary conservation of the interaction was established by showing the P. vivax P12 and P41 orthologs also heterodimerize.\",\n      \"evidence\": \"AVEXIS interaction assay with recombinant ectodomains in P. vivax\",\n      \"pmids\": [\"26701602\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Conservation of function, not just binding, remains unaddressed\", \"In vivo relevance in P. vivax untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The high-resolution architecture and druggability of the complex were resolved, defining two interfaces required for assembly and demonstrating that assembly can be blocked pharmacologically.\",\n      \"evidence\": \"X-ray crystallography of the Pf12-P41 complex at 2.85 Å, interface mutagenesis, and nanobody-mediated inhibition of complex formation in P. falciparum\",\n      \"pmids\": [\"35308105\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Biological consequence of blocking the complex not demonstrated\", \"No downstream effector or ligand identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biological function of the P12-P41 complex remains unknown: it is surface-localized, secreted after invasion, and non-adhesive, but no effector activity, ligand, or phenotype tied to its loss has been identified.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No demonstrated function for the secreted complex\", \"Proposed immune-evasion or redundant role untested\", \"No genetic redundancy experiment with sibling Cys6 proteins\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [1, 2, 3, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0045121\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0046658\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"Pf12-P41 heterodimer\"],\n    \"partners\": [\"P12 (Pf12)\"],\n    \"other_free_text\": [\n      \"GPI-anchored six-cysteine (Cys6) family merozoite surface antigen [#0]\",\n      \"Recognized by antibodies from naturally infected individuals [#0]\",\n      \"Complex secreted following erythrocyte invasion [#1]\",\n      \"Dispensable for asexual blood-stage replication in P. falciparum [#1] and P. berghei [#5]\",\n      \"Not an erythrocyte-receptor-binding adhesin; antisera do not substantially inhibit invasion [#7]\",\n      \"P12-P41 interaction conserved in P. vivax orthologs [#4]\",\n      \"Two interfaces required for complex formation; assembly blockable by anti-Pf12 nanobodies [#6]\",\n      \"Antiparallel subunit orientation inferred from cross-linking MS [#3]\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0404900","name":null,"product":"6-cysteine protein P41","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1002600","name":null,"product":"6-cysteine protein P41, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0303000","name":null,"product":"6-cysteine protein P41","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"P41","evaluation":null}