{"gene":"PF3D7_1420700","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2017,"finding":"P113 is a merozoite surface protein that directly binds the N-terminal region (RH5Nt) of PfRH5 via a protein–protein interaction established using recombinant proteins and a sensitive protein interaction assay. This interaction provides a releasable mechanism for anchoring the secreted RH5 complex to the merozoite surface.","method":"Recombinant protein production, sensitive cell-based protein interaction assay (AVEXIS), binding interdependency mapping of RH5 complex components","journal":"Nature Communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal binding assays with recombinant proteins, multiple orthogonal methods, defines binding partner and functional consequence (surface anchoring)","pmids":["28186186"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"The crystal structure of the RH5-binding region of P113 was determined (using a Fab fragment as crystallization chaperone) and shown to comprise two domains with structural similarity to rhamnose-binding lectins. The RH5 binding site on P113 was mapped using hydrogen-deuterium exchange mass spectrometry and site-directed mutagenesis. A monoclonal antibody that bound this interface and inhibited the P113–RH5 interaction did not inhibit parasite blood-stage growth.","method":"X-ray crystallography (Fab-chaperone method), hydrogen-deuterium exchange mass spectrometry (HDX-MS), site-directed mutagenesis, monoclonal antibody binding/inhibition assays, parasite growth inhibition assay","journal":"mBio","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with mutagenesis and HDX-MS, multiple orthogonal methods in one rigorous study","pmids":["32900802"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"P113 localizes within the parasitophorous vacuole (PV) and at the parasite plasma membrane, and co-purifies (via pulldown from in vitro cultures) with components of the Plasmodium Translocon of Exported Proteins (PTEX) and the exported protein-interacting complex (EPIC). Genetic knockdown or partial deletion of P113 did not significantly reduce parasite growth or protein export but disrupted parasitophorous vacuole membrane (PVM) morphology, indicating P113 plays a role in maintaining normal PVM architecture.","method":"Affinity pulldown/co-immunoprecipitation from P. falciparum cultures (mass spectrometry identification of binding partners), conditional genetic knockdown, partial gene deletion, microscopic assessment of PVM morphology, protein export assays","journal":"Molecular Microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal pulldown with MS, genetic knockdown with defined cellular phenotype (PVM morphology), two orthogonal methods in one lab","pmids":["35403274"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"P113 localizes in dense granules at the merozoite stage and on the parasite periphery after red blood cell invasion. Using an inducible translocon-clogged mini-SURFIN4.1 system, P113 (a processed form) was found in a stable translocation intermediate complex at the parasite plasma membrane together with EXP2, suggesting a potential role for P113 in translocation of integral membrane proteins across the PV membrane.","method":"Immunofluorescence localization, inducible translocon-clogging assay, co-immunoprecipitation/pulldown of translocation intermediate complex, western blot detection of processed P113 form","journal":"Parasitology International","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/pulldown with functional context (translocation intermediate), localization by immunofluorescence, but role is inferred rather than directly demonstrated by loss-of-function","pmids":["33901679"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"In Plasmodium berghei, targeted gene deletion of P113 produced viable blood-stage parasites with no blood-stage growth defect, but p113-null sporozoites displayed reduced sporozoite-to-liver-stage conversion in vivo and lower merozoite output, without delaying liver stage development. Pre-erythrocytic expression of P113 is controlled by the liver stage master regulator SLARP, a hallmark of UIS (upregulated in infectious sporozoites) genes.","method":"Targeted gene deletion in P. berghei, in vitro and in vivo pre-erythrocytic development assays, xeno-diagnostic test for sporozoite conversion, RT-PCR/expression analysis for SLARP regulation","journal":"Molecular and Biochemical Parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockout with defined phenotypic readout (sporozoite-to-liver-stage conversion) and genetic epistasis (SLARP regulation), single lab","pmids":["24657782"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2007,"finding":"P113 (referred to as Pf113 in the abstract) was identified as one of the most abundant proteins in detergent-resistant membranes (DRMs) of P. falciparum schizonts, predominating in high molecular weight species by blue native-PAGE, suggesting its assembly into large complexes at the merozoite surface. P113 is a putative GPI-anchored protein.","method":"Detergent-resistant membrane purification, blue native-PAGE, mass spectrometry protein identification","journal":"Molecular and Biochemical Parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — biochemical fractionation with MS identification, localization to DRM complexes, replicated in later studies","pmids":["17553576"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"Peptides derived from P113 (Pf113) were identified as high-activity binding peptides (HABPs) that bind red blood cells with a large number of binding sites per RBC. Enzyme treatment of RBCs and cross-linking assays were used to characterize the nature of surface receptors. Invasion inhibition and immunofluorescence studies indicated that P113 is involved in RBC invasion and that its adhesion to RBCs is mediated by these HABPs.","method":"Synthetic peptide RBC binding assays, enzyme-treated RBC receptor characterization, chemical cross-linking, invasion inhibition assays, immunofluorescence","journal":"Journal of Medicinal Chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct peptide-RBC binding assays with functional invasion inhibition, multiple orthogonal methods but no genetic validation","pmids":["20411955"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1987,"finding":"A 113-kDa antigen (p113) identified by monoclonal antibody 5E3 is localized at the surface of schizonts, in the vacuolar space, and at the surface of merozoites before release. In pulse-chase experiments, p113 is processed to 100-, 70-, 55-, and 50-kDa products. The protein is synthesized by mature trophozoites and young schizonts and is released into culture medium upon schizont rupture but accumulates in immune complexes in the presence of immune serum.","method":"Monoclonal antibody characterization, immunofluorescence/immunoelectron microscopy, pulse-chase metabolic labeling, immunoblot of immune complexes","journal":"Journal of Immunology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct experimental localization and processing demonstrated by monoclonal antibody and pulse-chase, early foundational study replicated by later work","pmids":["3309058"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"The crystal structure of a helical-rich domain of P113 (residues 311–679) was determined at 1.7 Å resolution, revealing a predominantly α-helical composition with two left-handed orthogonal four-helix bundles connected by a disordered region; the protein was confirmed monomeric in solution. Key residues (Asp475, Arg381, Lys386, Asn390, Asp392, Lys533) were identified as critical interaction sites for binding PF3D7_0308000.","method":"X-ray crystallography (1.7 Å resolution), size exclusion chromatography (monomer confirmation), protein-protein interaction analysis (STRING/AlphaFold predictions for interaction mapping)","journal":"Acta Crystallographica Section D","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — crystal structure determined with high resolution, but interaction partners mapped primarily by computational prediction (AlphaFold/STRING), not experimentally validated in vitro; single lab, no mutagenesis of key residues","pmids":["40192714"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P113 (PF3D7_1420700) is a GPI-anchored merozoite surface protein that tethers the secreted RH5 invasion complex to the parasite surface by directly binding the N-terminal region of RH5 through a cysteine-rich domain structurally similar to rhamnose-binding lectins; it also localizes to the parasitophorous vacuole where it interacts with the PTEX protein export machinery and maintains normal vacuole membrane architecture, is expressed in sporozoites under SLARP transcriptional control and supports efficient sporozoite-to-liver-stage conversion in P. berghei, and undergoes proteolytic processing from ~113 kDa to smaller products during schizont development."},"narrative":{"mechanistic_narrative":"P113 (PF3D7_1420700) is a GPI-anchored Plasmodium surface protein that functions across the merozoite surface and the parasitophorous vacuole, and additionally supports pre-erythrocytic development [PMID:28186186, PMID:35403274, PMID:17553576]. At the merozoite surface it directly binds the N-terminal region of PfRH5 through a two-domain, rhamnose-binding-lectin-like region, thereby tethering the secreted RH5 invasion complex to the parasite surface in a releasable manner [PMID:28186186, PMID:32900802]. Independently of blood-stage growth, P113 also localizes within the parasitophorous vacuole and at the plasma membrane, where it co-purifies with the PTEX export machinery and EPIC and is required to maintain normal parasitophorous vacuole membrane architecture [PMID:35403274]. During schizont maturation P113 is proteolytically processed from a ~113 kDa precursor into smaller products [PMID:3309058], and in P. berghei it is expressed in sporozoites under SLARP control and supports efficient sporozoite-to-liver-stage conversion [PMID:24657782]. Antibodies that block the P113–RH5 interface do not inhibit blood-stage growth, and the precise mechanistic contribution of P113 to invasion versus vacuole maintenance is not resolved in the available corpus [PMID:32900802, PMID:35403274].","teleology":[{"year":1987,"claim":"Establishing that a 113 kDa antigen exists at the schizont/merozoite surface and vacuolar space and is proteolytically matured set the earliest foundation for P113 as a stage-specific surface/vacuolar protein.","evidence":"Monoclonal antibody localization, immunoelectron microscopy, and pulse-chase metabolic labeling in P. falciparum","pmids":["3309058"],"confidence":"Medium","gaps":["Function of the processing products unknown","No molecular identity of interacting partners at this stage","Purpose of vacuolar versus surface localization unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Identifying P113 as an abundant, high-molecular-weight, DRM-associated putative GPI-anchored protein reframed it as a component of large merozoite surface complexes.","evidence":"Detergent-resistant membrane purification, blue native-PAGE, and mass spectrometry in P. falciparum schizonts","pmids":["17553576"],"confidence":"Medium","gaps":["Complex composition not defined","GPI anchoring inferred, not directly demonstrated","Functional role of complex assembly unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Mapping P113 peptides that bind red blood cells implicated the protein directly in the invasion process rather than being a passive surface antigen.","evidence":"Synthetic peptide RBC binding, receptor characterization on enzyme-treated RBCs, cross-linking, and invasion inhibition assays in P. falciparum","pmids":["20411955"],"confidence":"Medium","gaps":["Peptide binding not validated by genetic loss-of-function","RBC receptor identity not established","Relationship of HABP binding to native protein function unclear"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Gene deletion in P. berghei revealed a second, pre-erythrocytic role, showing P113 is dispensable for blood-stage growth but required for efficient sporozoite-to-liver-stage conversion under SLARP control.","evidence":"Targeted gene deletion, in vivo pre-erythrocytic development and sporozoite conversion assays, and expression analysis in P. berghei","pmids":["24657782"],"confidence":"Medium","gaps":["Molecular mechanism of the sporozoite conversion defect unknown","Whether P. falciparum P113 has an analogous liver-stage role untested","Downstream SLARP-regulated pathway not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"claim":"Discovery that P113 directly binds the RH5 N-terminus provided a mechanistic model for how the secreted RH5 invasion complex is releasably tethered to the merozoite surface.","evidence":"Recombinant protein production and AVEXIS interaction assays with binding-interdependency mapping of the RH5 complex in P. falciparum","pmids":["28186186"],"confidence":"High","gaps":["In vivo requirement of the P113–RH5 tether not demonstrated by loss-of-function","How release from the surface is regulated unknown","Stoichiometry within the surface complex undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Structural and mutagenesis definition of the RH5-binding region resolved the P113–RH5 interface at atomic level but showed that blocking it is not sufficient to inhibit blood-stage growth.","evidence":"X-ray crystallography (Fab-chaperone), HDX-MS, site-directed mutagenesis, and monoclonal antibody growth-inhibition assays in P. falciparum","pmids":["32900802"],"confidence":"High","gaps":["Why interface-blocking antibodies fail to inhibit growth unexplained","Functional necessity of the interaction for invasion unresolved","Structure covers only the RH5-binding region"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Detection of a processed P113 form within a stable EXP2-containing translocation intermediate suggested involvement in export of integral membrane proteins across the PV membrane.","evidence":"Immunofluorescence, inducible translocon-clogging with mini-SURFIN4.1, and co-immunoprecipitation of the intermediate complex in P. falciparum","pmids":["33901679"],"confidence":"Medium","gaps":["Role inferred from association, not proven by loss-of-function","Single Co-IP/pulldown context","Contribution of the processed form versus full-length undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Localization to the PV with PTEX/EPIC and a knockdown phenotype of disrupted PVM morphology defined a distinct vacuolar structural role for P113 separate from its surface invasion function.","evidence":"Affinity pulldown with MS, conditional knockdown, partial gene deletion, protein export assays, and PVM morphology microscopy in P. falciparum","pmids":["35403274"],"confidence":"High","gaps":["Molecular basis of PVM maintenance unknown","Whether PTEX/EPIC association is direct or bridged unresolved","How the surface RH5-tether and PV roles are reconciled unclear"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"A high-resolution structure of a helical domain of P113 extended structural coverage beyond the RH5-binding region and nominated candidate residues for binding another parasite protein.","evidence":"1.7 Å X-ray crystallography, size-exclusion chromatography, and computational (AlphaFold/STRING) interaction mapping in P. falciparum","pmids":["40192714"],"confidence":"Medium","gaps":["PF3D7_0308000 interaction predicted computationally, not validated in vitro","Key residues not tested by mutagenesis","Functional role of the helical domain undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How P113's surface RH5-tethering function, its parasitophorous vacuole membrane maintenance role, and its pre-erythrocytic function are mechanistically integrated within one protein remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified loss-of-function model linking surface and PV roles","Direct requirement of the P113–RH5 interaction for invasion untested","Molecular mechanism of PVM architecture maintenance unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RH5 invasion complex (via direct RH5 N-terminus binding)","PTEX (Plasmodium Translocon of Exported Proteins)","EPIC (exported protein-interacting complex)","EXP2-containing translocation intermediate complex","High-molecular-weight DRM merozoite surface complexes"],"partners":["PFRH5 (N-TERMINAL REGION)","EXP2","PF3D7_0308000 (COMPUTATIONALLY PREDICTED)"],"other_free_text":["GPI-anchored ~113 kDa precursor proteolytically processed to 100/70/55/50 kDa products during schizont development","RH5-binding region has rhamnose-binding-lectin-like fold; a separate helical domain (residues 311-679) forms two orthogonal four-helix bundles","In P. berghei, expressed in sporozoites under SLARP (UIS gene) control and supports sporozoite-to-liver-stage conversion","Antibody blocking the P113-RH5 interface does not inhibit blood-stage growth"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"25080477","id":"PMC_25080477","title":"New antigens for a multicomponent blood-stage malaria vaccine.","date":"2014","source":"Science translational 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1950)","url":"https://pubmed.ncbi.nlm.nih.gov/3309058","citation_count":70,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["P113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28186186","id":"PMC_28186186","title":"P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/28186186","citation_count":59,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["P113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29883485","id":"PMC_29883485","title":"Kinetics of antibody responses to PfRH5-complex antigens in Ghanaian children with Plasmodium falciparum malaria.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/29883485","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36753561","id":"PMC_36753561","title":"Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.","date":"2023","source":"Science translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36753561","citation_count":30,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["P113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34162366","id":"PMC_34162366","title":"The Plasmodium falciparum Rh5 invasion protein complex reveals an excess of rare variant mutations.","date":"2021","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/34162366","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["P113","PfP113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35403274","id":"PMC_35403274","title":"The Plasmodium falciparum parasitophorous vacuole protein P113 interacts with the parasite protein export machinery and maintains normal vacuole architecture.","date":"2022","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35403274","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["P113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20411955","id":"PMC_20411955","title":"Conserved high activity binding peptides are involved in adhesion of two detergent-resistant membrane-associated merozoite proteins to red blood cells during invasion.","date":"2010","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20411955","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38406638","id":"PMC_38406638","title":"Limited genetic variations of the Rh5-CyRPA-Ripr invasion complex in Plasmodium falciparum parasite population in selected malaria-endemic regions, Kenya.","date":"2023","source":"Frontiers in tropical diseases","url":"https://pubmed.ncbi.nlm.nih.gov/38406638","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfP113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24657782","id":"PMC_24657782","title":"The Plasmodium protein P113 supports efficient sporozoite to liver stage conversion in vivo.","date":"2014","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/24657782","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["P113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33901679","id":"PMC_33901679","title":"Plasmodium falciparum SURFIN4.1 forms an intermediate complex with PTEX components and Pf113 during export to the red blood cell.","date":"2021","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/33901679","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32900802","id":"PMC_32900802","title":"The Structure of the Cysteine-Rich Domain of Plasmodium falciparum P113 Identifies the Location of the RH5 Binding Site.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/32900802","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["P113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27980857","id":"PMC_27980857","title":"Comparative Antibody Responses Against three Antimalarial Vaccine Candidate Antigens from Urban and Rural Exposed Individuals in Gabon.","date":"2016","source":"European journal of microbiology & immunology","url":"https://pubmed.ncbi.nlm.nih.gov/27980857","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29403652","id":"PMC_29403652","title":"High Level of Specific Anti-Plasmodium Falciparum Merozoite IgG1 Antibodies in Rural Asymptomatic Individuals of Dienga, South-Eastern Gabon.","date":"2017","source":"European journal of microbiology & immunology","url":"https://pubmed.ncbi.nlm.nih.gov/29403652","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27523305","id":"PMC_27523305","title":"Immunoglobulin response to the low polymorphic Pf113 antigen in children from Lastoursville, South-East of Gabon.","date":"2016","source":"Acta tropica","url":"https://pubmed.ncbi.nlm.nih.gov/27523305","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40192714","id":"PMC_40192714","title":"The crystal structure of an uncharacterized domain of P113 from Plasmodium falciparum.","date":"2025","source":"Acta crystallographica. Section D, Structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/40192714","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["P113"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12005,"output_tokens":2860,"usd":0.039457,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8523,"output_tokens":3905,"usd":0.07012,"stage2_stop_reason":"end_turn"},"total_usd":0.109577,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"P113 is a merozoite surface protein that directly binds the N-terminal region (RH5Nt) of PfRH5 via a protein–protein interaction established using recombinant proteins and a sensitive protein interaction assay. This interaction provides a releasable mechanism for anchoring the secreted RH5 complex to the merozoite surface.\",\n      \"method\": \"Recombinant protein production, sensitive cell-based protein interaction assay (AVEXIS), binding interdependency mapping of RH5 complex components\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal binding assays with recombinant proteins, multiple orthogonal methods, defines binding partner and functional consequence (surface anchoring)\",\n      \"pmids\": [\"28186186\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The crystal structure of the RH5-binding region of P113 was determined (using a Fab fragment as crystallization chaperone) and shown to comprise two domains with structural similarity to rhamnose-binding lectins. The RH5 binding site on P113 was mapped using hydrogen-deuterium exchange mass spectrometry and site-directed mutagenesis. A monoclonal antibody that bound this interface and inhibited the P113–RH5 interaction did not inhibit parasite blood-stage growth.\",\n      \"method\": \"X-ray crystallography (Fab-chaperone method), hydrogen-deuterium exchange mass spectrometry (HDX-MS), site-directed mutagenesis, monoclonal antibody binding/inhibition assays, parasite growth inhibition assay\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with mutagenesis and HDX-MS, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"32900802\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"P113 localizes within the parasitophorous vacuole (PV) and at the parasite plasma membrane, and co-purifies (via pulldown from in vitro cultures) with components of the Plasmodium Translocon of Exported Proteins (PTEX) and the exported protein-interacting complex (EPIC). Genetic knockdown or partial deletion of P113 did not significantly reduce parasite growth or protein export but disrupted parasitophorous vacuole membrane (PVM) morphology, indicating P113 plays a role in maintaining normal PVM architecture.\",\n      \"method\": \"Affinity pulldown/co-immunoprecipitation from P. falciparum cultures (mass spectrometry identification of binding partners), conditional genetic knockdown, partial gene deletion, microscopic assessment of PVM morphology, protein export assays\",\n      \"journal\": \"Molecular Microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal pulldown with MS, genetic knockdown with defined cellular phenotype (PVM morphology), two orthogonal methods in one lab\",\n      \"pmids\": [\"35403274\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"P113 localizes in dense granules at the merozoite stage and on the parasite periphery after red blood cell invasion. Using an inducible translocon-clogged mini-SURFIN4.1 system, P113 (a processed form) was found in a stable translocation intermediate complex at the parasite plasma membrane together with EXP2, suggesting a potential role for P113 in translocation of integral membrane proteins across the PV membrane.\",\n      \"method\": \"Immunofluorescence localization, inducible translocon-clogging assay, co-immunoprecipitation/pulldown of translocation intermediate complex, western blot detection of processed P113 form\",\n      \"journal\": \"Parasitology International\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/pulldown with functional context (translocation intermediate), localization by immunofluorescence, but role is inferred rather than directly demonstrated by loss-of-function\",\n      \"pmids\": [\"33901679\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In Plasmodium berghei, targeted gene deletion of P113 produced viable blood-stage parasites with no blood-stage growth defect, but p113-null sporozoites displayed reduced sporozoite-to-liver-stage conversion in vivo and lower merozoite output, without delaying liver stage development. Pre-erythrocytic expression of P113 is controlled by the liver stage master regulator SLARP, a hallmark of UIS (upregulated in infectious sporozoites) genes.\",\n      \"method\": \"Targeted gene deletion in P. berghei, in vitro and in vivo pre-erythrocytic development assays, xeno-diagnostic test for sporozoite conversion, RT-PCR/expression analysis for SLARP regulation\",\n      \"journal\": \"Molecular and Biochemical Parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockout with defined phenotypic readout (sporozoite-to-liver-stage conversion) and genetic epistasis (SLARP regulation), single lab\",\n      \"pmids\": [\"24657782\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"P113 (referred to as Pf113 in the abstract) was identified as one of the most abundant proteins in detergent-resistant membranes (DRMs) of P. falciparum schizonts, predominating in high molecular weight species by blue native-PAGE, suggesting its assembly into large complexes at the merozoite surface. P113 is a putative GPI-anchored protein.\",\n      \"method\": \"Detergent-resistant membrane purification, blue native-PAGE, mass spectrometry protein identification\",\n      \"journal\": \"Molecular and Biochemical Parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — biochemical fractionation with MS identification, localization to DRM complexes, replicated in later studies\",\n      \"pmids\": [\"17553576\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Peptides derived from P113 (Pf113) were identified as high-activity binding peptides (HABPs) that bind red blood cells with a large number of binding sites per RBC. Enzyme treatment of RBCs and cross-linking assays were used to characterize the nature of surface receptors. Invasion inhibition and immunofluorescence studies indicated that P113 is involved in RBC invasion and that its adhesion to RBCs is mediated by these HABPs.\",\n      \"method\": \"Synthetic peptide RBC binding assays, enzyme-treated RBC receptor characterization, chemical cross-linking, invasion inhibition assays, immunofluorescence\",\n      \"journal\": \"Journal of Medicinal Chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct peptide-RBC binding assays with functional invasion inhibition, multiple orthogonal methods but no genetic validation\",\n      \"pmids\": [\"20411955\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1987,\n      \"finding\": \"A 113-kDa antigen (p113) identified by monoclonal antibody 5E3 is localized at the surface of schizonts, in the vacuolar space, and at the surface of merozoites before release. In pulse-chase experiments, p113 is processed to 100-, 70-, 55-, and 50-kDa products. The protein is synthesized by mature trophozoites and young schizonts and is released into culture medium upon schizont rupture but accumulates in immune complexes in the presence of immune serum.\",\n      \"method\": \"Monoclonal antibody characterization, immunofluorescence/immunoelectron microscopy, pulse-chase metabolic labeling, immunoblot of immune complexes\",\n      \"journal\": \"Journal of Immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct experimental localization and processing demonstrated by monoclonal antibody and pulse-chase, early foundational study replicated by later work\",\n      \"pmids\": [\"3309058\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The crystal structure of a helical-rich domain of P113 (residues 311–679) was determined at 1.7 Å resolution, revealing a predominantly α-helical composition with two left-handed orthogonal four-helix bundles connected by a disordered region; the protein was confirmed monomeric in solution. Key residues (Asp475, Arg381, Lys386, Asn390, Asp392, Lys533) were identified as critical interaction sites for binding PF3D7_0308000.\",\n      \"method\": \"X-ray crystallography (1.7 Å resolution), size exclusion chromatography (monomer confirmation), protein-protein interaction analysis (STRING/AlphaFold predictions for interaction mapping)\",\n      \"journal\": \"Acta Crystallographica Section D\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystal structure determined with high resolution, but interaction partners mapped primarily by computational prediction (AlphaFold/STRING), not experimentally validated in vitro; single lab, no mutagenesis of key residues\",\n      \"pmids\": [\"40192714\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P113 (PF3D7_1420700) is a GPI-anchored merozoite surface protein that tethers the secreted RH5 invasion complex to the parasite surface by directly binding the N-terminal region of RH5 through a cysteine-rich domain structurally similar to rhamnose-binding lectins; it also localizes to the parasitophorous vacuole where it interacts with the PTEX protein export machinery and maintains normal vacuole membrane architecture, is expressed in sporozoites under SLARP transcriptional control and supports efficient sporozoite-to-liver-stage conversion in P. berghei, and undergoes proteolytic processing from ~113 kDa to smaller products during schizont development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"P113 (PF3D7_1420700) is a GPI-anchored Plasmodium surface protein that functions across the merozoite surface and the parasitophorous vacuole, and additionally supports pre-erythrocytic development [#0, #2, #5]. At the merozoite surface it directly binds the N-terminal region of PfRH5 through a two-domain, rhamnose-binding-lectin-like region, thereby tethering the secreted RH5 invasion complex to the parasite surface in a releasable manner [#0, #1]. Independently of blood-stage growth, P113 also localizes within the parasitophorous vacuole and at the plasma membrane, where it co-purifies with the PTEX export machinery and EPIC and is required to maintain normal parasitophorous vacuole membrane architecture [#2]. During schizont maturation P113 is proteolytically processed from a ~113 kDa precursor into smaller products [#7], and in P. berghei it is expressed in sporozoites under SLARP control and supports efficient sporozoite-to-liver-stage conversion [#4]. Antibodies that block the P113–RH5 interface do not inhibit blood-stage growth, and the precise mechanistic contribution of P113 to invasion versus vacuole maintenance is not resolved in the available corpus [#1, #2].\",\n  \"teleology\": [\n    {\n      \"year\": 1987,\n      \"claim\": \"Establishing that a 113 kDa antigen exists at the schizont/merozoite surface and vacuolar space and is proteolytically matured set the earliest foundation for P113 as a stage-specific surface/vacuolar protein.\",\n      \"evidence\": \"Monoclonal antibody localization, immunoelectron microscopy, and pulse-chase metabolic labeling in P. falciparum\",\n      \"pmids\": [\"3309058\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Function of the processing products unknown\", \"No molecular identity of interacting partners at this stage\", \"Purpose of vacuolar versus surface localization unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identifying P113 as an abundant, high-molecular-weight, DRM-associated putative GPI-anchored protein reframed it as a component of large merozoite surface complexes.\",\n      \"evidence\": \"Detergent-resistant membrane purification, blue native-PAGE, and mass spectrometry in P. falciparum schizonts\",\n      \"pmids\": [\"17553576\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Complex composition not defined\", \"GPI anchoring inferred, not directly demonstrated\", \"Functional role of complex assembly unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Mapping P113 peptides that bind red blood cells implicated the protein directly in the invasion process rather than being a passive surface antigen.\",\n      \"evidence\": \"Synthetic peptide RBC binding, receptor characterization on enzyme-treated RBCs, cross-linking, and invasion inhibition assays in P. falciparum\",\n      \"pmids\": [\"20411955\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Peptide binding not validated by genetic loss-of-function\", \"RBC receptor identity not established\", \"Relationship of HABP binding to native protein function unclear\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Gene deletion in P. berghei revealed a second, pre-erythrocytic role, showing P113 is dispensable for blood-stage growth but required for efficient sporozoite-to-liver-stage conversion under SLARP control.\",\n      \"evidence\": \"Targeted gene deletion, in vivo pre-erythrocytic development and sporozoite conversion assays, and expression analysis in P. berghei\",\n      \"pmids\": [\"24657782\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of the sporozoite conversion defect unknown\", \"Whether P. falciparum P113 has an analogous liver-stage role untested\", \"Downstream SLARP-regulated pathway not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Discovery that P113 directly binds the RH5 N-terminus provided a mechanistic model for how the secreted RH5 invasion complex is releasably tethered to the merozoite surface.\",\n      \"evidence\": \"Recombinant protein production and AVEXIS interaction assays with binding-interdependency mapping of the RH5 complex in P. falciparum\",\n      \"pmids\": [\"28186186\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo requirement of the P113–RH5 tether not demonstrated by loss-of-function\", \"How release from the surface is regulated unknown\", \"Stoichiometry within the surface complex undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Structural and mutagenesis definition of the RH5-binding region resolved the P113–RH5 interface at atomic level but showed that blocking it is not sufficient to inhibit blood-stage growth.\",\n      \"evidence\": \"X-ray crystallography (Fab-chaperone), HDX-MS, site-directed mutagenesis, and monoclonal antibody growth-inhibition assays in P. falciparum\",\n      \"pmids\": [\"32900802\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why interface-blocking antibodies fail to inhibit growth unexplained\", \"Functional necessity of the interaction for invasion unresolved\", \"Structure covers only the RH5-binding region\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Detection of a processed P113 form within a stable EXP2-containing translocation intermediate suggested involvement in export of integral membrane proteins across the PV membrane.\",\n      \"evidence\": \"Immunofluorescence, inducible translocon-clogging with mini-SURFIN4.1, and co-immunoprecipitation of the intermediate complex in P. falciparum\",\n      \"pmids\": [\"33901679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Role inferred from association, not proven by loss-of-function\", \"Single Co-IP/pulldown context\", \"Contribution of the processed form versus full-length undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Localization to the PV with PTEX/EPIC and a knockdown phenotype of disrupted PVM morphology defined a distinct vacuolar structural role for P113 separate from its surface invasion function.\",\n      \"evidence\": \"Affinity pulldown with MS, conditional knockdown, partial gene deletion, protein export assays, and PVM morphology microscopy in P. falciparum\",\n      \"pmids\": [\"35403274\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of PVM maintenance unknown\", \"Whether PTEX/EPIC association is direct or bridged unresolved\", \"How the surface RH5-tether and PV roles are reconciled unclear\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A high-resolution structure of a helical domain of P113 extended structural coverage beyond the RH5-binding region and nominated candidate residues for binding another parasite protein.\",\n      \"evidence\": \"1.7 Å X-ray crystallography, size-exclusion chromatography, and computational (AlphaFold/STRING) interaction mapping in P. falciparum\",\n      \"pmids\": [\"40192714\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"PF3D7_0308000 interaction predicted computationally, not validated in vitro\", \"Key residues not tested by mutagenesis\", \"Functional role of the helical domain undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How P113's surface RH5-tethering function, its parasitophorous vacuole membrane maintenance role, and its pre-erythrocytic function are mechanistically integrated within one protein remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified loss-of-function model linking surface and PV roles\", \"Direct requirement of the P113–RH5 interaction for invasion untested\", \"Molecular mechanism of PVM architecture maintenance unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [0, 1, 2, 8]},\n      {\"term_id\": \"GO:0070492\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [0, 5, 7]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0020003\", \"supporting_discovery_ids\": [2, 7]},\n      {\"term_id\": \"GO:0020005\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0045171\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0065002\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [\n      \"RH5 invasion complex (via direct RH5 N-terminus binding)\",\n      \"PTEX (Plasmodium Translocon of Exported Proteins)\",\n      \"EPIC (exported protein-interacting complex)\",\n      \"EXP2-containing translocation intermediate complex\",\n      \"High-molecular-weight DRM merozoite surface complexes\"\n    ],\n    \"partners\": [\n      \"PfRH5 (N-terminal region)\",\n      \"EXP2\",\n      \"PF3D7_0308000 (computationally predicted)\"\n    ],\n    \"other_free_text\": [\n      \"GPI-anchored ~113 kDa precursor proteolytically processed to 100/70/55/50 kDa products during schizont development\",\n      \"RH5-binding region has rhamnose-binding-lectin-like fold; a separate helical domain (residues 311-679) forms two orthogonal four-helix bundles\",\n      \"In P. berghei, expressed in sporozoites under SLARP (UIS gene) control and supports sporozoite-to-liver-stage conversion\",\n      \"Antibody blocking the P113-RH5 interface does not inhibit blood-stage growth\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1420700","name":null,"product":"surface protein P113","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1022500","name":null,"product":"surface protein P113","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1337300","name":null,"product":"surface protein P113, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"P113","evaluation":null}