{"gene":"PF3D7_1016300","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":1984,"finding":"GBP130 (130 kDa protein) is located on the merozoite surface coat and binds to glycophorin (erythrocyte sialoglycoprotein) in a saturable manner; antibodies against it inhibit merozoite invasion into erythrocytes and inhibit binding of the protein to a glycophorin-matrix.","method":"Glycophorin-coupled acrylamide matrix affinity binding assay, immunoelectron microscopy, invasion inhibition assay","journal":"The Journal of experimental medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assay and invasion inhibition with antibodies, immunoelectron microscopy for localization, single lab with multiple orthogonal methods","pmids":["6206188"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1985,"finding":"The GBP130 gene was cloned and the primary sequence reveals a 150-nucleotide tandem-repeating sequence coding for a 50-amino-acid repeat; recombinant protein expressing these repeats interacts with glycophorin.","method":"cDNA cloning and sequencing, recombinant protein expression in E. coli, binding assay","journal":"Science (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gene cloning with sequence characterization and recombinant binding assay, single lab, two orthogonal methods","pmids":["3883491"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1986,"finding":"The glycophorin-binding domain of GBP130 resides in the tandemly repeated 50-amino-acid sequence (11 highly conserved copies); binding to glycophorin correlates with repeat number, and antibodies directed against the repeat sequence inhibit in vitro erythrocyte invasion by merozoites.","method":"Gene cloning and sequencing, recombinant protein expression of varying repeat numbers, glycophorin-binding assay, invasion inhibition with repeat-specific antibodies","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — recombinant domain mapping with mutagenesis-equivalent repeat-number variation, direct binding assay, functional antibody inhibition; replicated by independent cloning study (PMID 3883491)","pmids":["3512098"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1987,"finding":"The glycophorin-binding specificity of GBP130 (and other proteins identified via glycophorin-coupled AE-BioGel) requires re-evaluation because the AE-BioGel matrix itself has strong ion-exchange properties that cause non-specific protein binding; this is a negative/cautionary result calling into question the specificity of the glycophorin-binding assay used to characterize GBP130.","method":"Glycophorin-coupled AE-BioGel binding assay with and without coupled glycophorin under varying ionic conditions","journal":"The Journal of experimental medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct experimental demonstration of matrix artifact, single lab but mechanistically informative negative result","pmids":["3298526"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1989,"finding":"GBP130 is accessible at the merozoite surface and is recognized by antibodies that inhibit merozoite dispersal from infected erythrocytes, as identified by probing 2D immunoblots with antibodies dissociated from immune complexes at the merozoite surface.","method":"Two-dimensional immunoblotting, antibody dissociation from immune complexes at merozoite surface","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct identification of surface-accessible antigen by antibody dissociation from immune complexes, single lab","pmids":["2509909"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1990,"finding":"GBP130 was NOT detected in crosslinked immune complexes with the major merozoite surface glycoprotein Pf200, indicating GBP130 does not form a stable proximal complex with Pf200 at the merozoite surface under these conditions.","method":"Chemical crosslinking with dithiobis(succinimidyl) propionate, immunoprecipitation, immunoblotting","journal":"Experimental parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method; negative result (GBP130 not detected in Pf200 crosslinked complexes)","pmids":["2404782"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1992,"finding":"The GBP130 gene resides within a cluster of three erythrocytic-stage transcription units on chromosome 10; nuclear run-on data demonstrate that transcription of GBP130 and its upstream neighbor is monocistronic despite being separated by less than 2 kb, with termination of the upstream gene and initiation of GBP130 occurring within this intergenic region.","method":"Yeast artificial chromosome (YAC) mapping, nuclear run-on transcription assay","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — nuclear run-on directly demonstrates monocistronic transcription and maps initiation/termination sites; single lab with two orthogonal methods","pmids":["1374714"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1999,"finding":"A discrete five base pair cis-acting sequence element within the GBP130 promoter is necessary for efficient promoter activity and binds nuclear factors in a sequence-specific manner; this element shares no homology with known eukaryotic transcription factor binding sites.","method":"Mutational analysis of promoter by deletion/substitution, reporter gene assay, electrophoretic mobility shift assay (EMSA) for nuclear factor binding","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — promoter mutagenesis combined with nuclear factor binding assay, single lab with two orthogonal methods","pmids":["10215026"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1999,"finding":"The GBP130 promoter loses its developmental (stage-specific) restriction and becomes constitutively active when placed on an episomal plasmid, coinciding with the absence of phased nucleosomal arrays over the episome, suggesting epigenetic (chromatin) regulation underlies the developmental control of GBP130 transcription.","method":"Transient transfection with episomal constructs, comparison with endogenous chromosomal promoter activity, nucleosome positioning analysis","journal":"Parasitology international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct comparison of episomal vs. chromosomal promoter activity linked to nucleosome organization, single lab with two orthogonal methods","pmids":["11269326"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2002,"finding":"The length of the 5' UTR of GBP130 regulates promoter activity in a stage-specific manner: a shorter 5' UTR is functional at ring stage, while a longer 5' UTR promotes transcription at trophozoite and schizont stages; poly(dA:dT) tracts in the proximal sequence enhance promoter strength.","method":"Promoter deletion constructs transfected into P. falciparum, CAT reporter gene expression measured by liquid scintillation counting at defined developmental stages","journal":"Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single reporter method, limited controls described in abstract","pmids":["12567560"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"finding":"The P. falciparum TATA-binding protein (PfTBP) associates with a TATA box-like sequence (TGTAA) at position -186 of the GBP130 gene promoter region in vitro and in vivo, as shown by supershift, DNase I footprinting with GST-PfTBP fusion protein, and chromatin immunoprecipitation.","method":"EMSA supershift assay, DNase I footprinting with GST-PfTBP fusion protein, chromatin immunoprecipitation (ChIP)","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — three orthogonal methods (EMSA, footprinting, ChIP) in a single lab demonstrating PfTBP binding to GBP130 promoter","pmids":["15760658"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"The extended N-terminal region of the GBP130 signal peptide is not required for directing the protein into the secretory pathway; multiple deletions of this N-terminal extension do not impair targeting of a fluorescent reporter to the secretory pathway, and the extension does not affect transport of soluble or membrane proteins to their correct subcellular localizations.","method":"Signal peptide deletion mutagenesis fused to fluorescent reporter, live-cell imaging of secretory pathway targeting in P. falciparum and mammalian cells","journal":"International journal of medical microbiology : IJMM","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct mutagenesis of signal peptide with functional reporter assay in P. falciparum and mammalian cells; single lab, multiple constructs and cell systems","pmids":["28750796"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"Antibodies targeting the GBP130-A region (aa 111-374) inhibit RBC invasion by P. falciparum in vitro when induced by mRNA or DNA immunogens, identifying this region as functionally important for invasion.","method":"Mouse immunization with lipid-encapsulated mRNA, DNA plasmid, and recombinant protein immunogens; in vitro growth inhibition/invasion inhibition assay","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro invasion inhibition assay with antisera against defined protein region; single lab with multiple immunogen formats","pmids":["38863702"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"GBP130 is expressed on the surface of P. falciparum-infected RBCs and directly binds the I-domain of LFA-1 (LFA-1 αI); it was identified as a high-confidence LFA-1 ligand by LC-MS/MS analysis of LFA-1 αI-Fc immunoprecipitates from iRBCs, and recombinant GBP130 binds NK and THP-1 cells in an LFA-1-dependent manner, promoting NK cell activation, degranulation, and contact-dependent killing of iRBCs.","method":"LFA-1 αI-Fc fusion protein pulldown, LC-MS/MS proteomics, recombinant protein binding assay, NK cell co-culture activation/degranulation assay, neutralizing antibody inhibition of NK killing","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (affinity pulldown + mass spectrometry identification + recombinant binding assay + functional co-culture assay + antibody neutralization) in a single study establishing GBP130 as the LFA-1 ligand on iRBCs","pmids":["42206825"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"GBP130 (PF3D7_1016300) is a P. falciparum merozoite surface protein whose tandemly repeated 50-amino-acid domain mediates binding to the erythrocyte receptor glycophorin in a repeat-number-dependent manner, facilitating RBC invasion; it is also expressed on the surface of infected RBCs where it serves as a ligand for the integrin LFA-1 on NK cells, promoting NK cell activation and parasite killing; its expression is regulated by a five-base-pair promoter element and phased nucleosomal arrays, with PfTBP binding a TATA box-like element in its promoter, and its extended signal peptide N-terminal region is dispensable for secretory pathway entry."},"narrative":{"mechanistic_narrative":"GBP130 (PF3D7_1016300) is a Plasmodium falciparum blood-stage protein that operates at the interface between the parasite and host erythrocytes and immune cells [PMID:6206188, PMID:42206825]. During merozoite invasion it localizes to the merozoite surface coat and binds the erythrocyte sialoglycoprotein glycophorin in a saturable manner; antibodies against it block both glycophorin binding and invasion [PMID:6206188]. Its glycophorin-binding activity is carried by a tandemly repeated 50-amino-acid sequence, and binding scales with the number of repeats, while repeat-specific antibodies inhibit erythrocyte invasion [PMID:3883491, PMID:3512098]; antibodies against a defined N-terminal region (aa 111-374) likewise inhibit invasion [PMID:38863702]. Transcription of GBP130 is developmentally controlled through cis-regulatory architecture on chromosome 10, including a five-base-pair promoter element that binds sequence-specific nuclear factors and a TATA box-like element bound by the P. falciparum TATA-binding protein PfTBP, with stage restriction linked to phased nucleosomal arrays over the endogenous locus [PMID:10215026, PMID:15760658, PMID:11269326]. Beyond its invasion role, GBP130 is displayed on the surface of infected RBCs, where it directly binds the I-domain of the integrin LFA-1 and drives LFA-1-dependent NK cell activation, degranulation, and contact-dependent killing of infected erythrocytes [PMID:42206825]. An early cautionary study showed the glycophorin-coupled AE-BioGel matrix used to define binding has intrinsic ion-exchange properties that can produce non-specific binding, qualifying the affinity-matrix data [PMID:3298526].","teleology":[{"year":1984,"claim":"Established that GBP130 is a merozoite-surface protein with a defined host-receptor binding activity, raising the possibility that it participates in erythrocyte invasion.","evidence":"Glycophorin-matrix affinity binding, immunoelectron microscopy, and antibody invasion-inhibition in P. falciparum","pmids":["6206188"],"confidence":"Medium","gaps":["Affinity-matrix binding later shown to be subject to non-specific artifact","No mapping of the binding domain at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1986,"claim":"Localized the glycophorin-binding function to a tandem 50-amino-acid repeat and showed binding depends on repeat number, defining the molecular basis of receptor engagement and its inhibition.","evidence":"cDNA cloning/sequencing and recombinant expression of variable repeat numbers with glycophorin binding and repeat-specific antibody invasion inhibition in P. falciparum","pmids":["3883491","3512098"],"confidence":"High","gaps":["Structural basis of repeat-glycophorin interaction unresolved","Contribution of non-repeat regions to invasion not defined here"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1987,"claim":"Questioned the specificity of the primary assay used to characterize GBP130 binding by showing the affinity matrix itself binds proteins non-specifically.","evidence":"Glycophorin-coupled AE-BioGel binding assay with and without glycophorin under varying ionic conditions in P. falciparum","pmids":["3298526"],"confidence":"Medium","gaps":["Does not overturn the antibody-based invasion inhibition data","Extent of artifact for GBP130 specifically not quantified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1990,"claim":"Tested whether GBP130 physically partners with the major merozoite surface glycoprotein Pf200 and found no stable proximal complex under crosslinking conditions.","evidence":"Chemical crosslinking, immunoprecipitation, and immunoblotting in P. falciparum","pmids":["2404782"],"confidence":"Low","gaps":["Single method negative result; absence of crosslinking does not exclude transient association","No reciprocal or alternative interaction screen"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1992,"claim":"Defined the genomic and transcriptional context of GBP130, showing it is monocistronically transcribed within a chromosome-10 gene cluster.","evidence":"YAC mapping and nuclear run-on transcription assay in P. falciparum","pmids":["1374714"],"confidence":"Medium","gaps":["Regulatory elements not yet identified","Functional consequence of the clustered arrangement unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1999,"claim":"Identified cis-regulatory and chromatin determinants of GBP130 expression, linking developmental stage restriction to a discrete promoter element and to phased nucleosomal arrays.","evidence":"Promoter mutagenesis with reporter assays and EMSA, plus episomal vs chromosomal promoter comparison with nucleosome positioning in P. falciparum","pmids":["10215026","11269326"],"confidence":"Medium","gaps":["Identity of the sequence-specific nuclear factor not determined","Mechanistic link between nucleosome phasing and stage timing not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2002,"claim":"Proposed that 5' UTR length and poly(dA:dT) tracts tune stage-specific promoter output for GBP130.","evidence":"Promoter/5' UTR deletion CAT reporter constructs at defined developmental stages in P. falciparum","pmids":["12567560"],"confidence":"Low","gaps":["Single reporter method with limited controls","Endogenous relevance of 5' UTR length variation not confirmed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"Placed GBP130 transcription within basal machinery by demonstrating PfTBP binding to a TATA box-like element in its promoter.","evidence":"EMSA supershift, DNase I footprinting with GST-PfTBP, and ChIP in P. falciparum","pmids":["15760658"],"confidence":"Medium","gaps":["Functional requirement of PfTBP occupancy for GBP130 expression not tested","Interplay with the five-base-pair element unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Dissected the unusually extended signal peptide and showed its N-terminal extension is dispensable for secretory-pathway entry.","evidence":"Signal peptide deletion mutagenesis fused to fluorescent reporters imaged in P. falciparum and mammalian cells","pmids":["28750796"],"confidence":"Medium","gaps":["Alternative function of the extended N-terminus not identified","No effect on trafficking of native full-length GBP130 tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Identified a discrete invasion-relevant epitope region (aa 111-374) whose antibodies block invasion, supporting GBP130 as a vaccine-relevant invasion antigen.","evidence":"Mouse immunization with mRNA, DNA, and recombinant protein immunogens and in vitro growth/invasion inhibition assays for P. falciparum","pmids":["38863702"],"confidence":"Medium","gaps":["Mechanism of inhibition by this region not defined","Receptor engaged by the aa 111-374 region not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Revealed a second, immune-facing role for GBP130 as an infected-RBC surface ligand for the LFA-1 integrin that triggers NK-cell killing of infected erythrocytes.","evidence":"LFA-1 alphaI-Fc pulldown with LC-MS/MS, recombinant binding assays, and NK/THP-1 co-culture activation, degranulation and neutralization assays with P. falciparum iRBCs","pmids":["42206825"],"confidence":"High","gaps":["Structural basis of GBP130-LFA-1 alphaI binding not resolved","How merozoite-surface GBP130 relates to iRBC-surface display not established","In vivo relevance of NK-mediated killing not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown how GBP130's two receptor engagements (glycophorin during invasion versus LFA-1 on the infected-RBC surface) are structurally and temporally coordinated, and whether the tandem repeat and the aa 111-374 region contribute to each function.","evidence":"No timeline discovery integrates the invasion and immune-ligand roles or provides a structural model","pmids":[],"confidence":"Low","gaps":["No structural model of any GBP130 domain","No genetic knockout/knockdown phenotype in the corpus","Domain assignment for LFA-1 binding not mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["GLYCOPHORIN (ERYTHROCYTE SIALOGLYCOPROTEIN) [#0, #1, #2]","LFA-1 INTEGRIN (ALPHAI/I-DOMAIN) [#13]","PFTBP (P. FALCIPARUM TATA-BINDING PROTEIN) [#10]"],"other_free_text":["Glycophorin-binding activity maps to a tandem 50-amino-acid repeat (11 conserved copies) and scales with repeat number [#2, #1].","aa 111-374 region antibodies inhibit invasion, marking it as functionally important [#12].","Extended N-terminal signal-peptide region is dispensable for secretory-pathway entry [#11].","GBP130 was not detected in crosslinked complexes with the major surface glycoprotein Pf200 [#5].","Early glycophorin affinity-matrix data are qualified by an ion-exchange artifact of the AE-BioGel matrix [#3].","Gene lies in a chromosome-10 cluster and is transcribed monocistronically; developmental control is linked to phased nucleosomal arrays and a five-base-pair promoter element [#6, #7, #8]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"3512098","id":"PMC_3512098","title":"A tandemly repeated sequence determines the binding domain for an erythrocyte receptor binding protein of P. falciparum.","date":"1986","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/3512098","citation_count":103,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GBP130"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"1374714","id":"PMC_1374714","title":"Transcription mapping of a 100 kb locus of Plasmodium falciparum identifies an intergenic region in which transcription terminates and reinitiates.","date":"1992","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/1374714","citation_count":92,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GBP130"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"6206188","id":"PMC_6206188","title":"Surface proteins of Plasmodium falciparum merozoites binding to the erythrocyte receptor, glycophorin.","date":"1984","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/6206188","citation_count":92,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"3883491","id":"PMC_3883491","title":"Isolation of the gene for a glycophorin-binding protein implicated in erythrocyte invasion by a malaria parasite.","date":"1985","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/3883491","citation_count":89,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2509909","id":"PMC_2509909","title":"Specificities of antibodies that inhibit merozoite dispersal from malaria-infected erythrocytes.","date":"1989","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2509909","citation_count":50,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GBP130"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"10215026","id":"PMC_10215026","title":"Mutational analysis identifies a five base pair cis-acting sequence essential for GBP130 promoter activity in Plasmodium falciparum.","date":"1999","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/10215026","citation_count":49,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GBP130"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15760658","id":"PMC_15760658","title":"Recombinant and native Plasmodium falciparum TATA-binding-protein binds to a specific TATA box element in promoter regions.","date":"2005","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15760658","citation_count":32,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GBP130"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"1684263","id":"PMC_1684263","title":"A study of the genomic diversity of Plasmodium falciparum in Senegal. 2. Typing by the use of the polymerase chain reaction.","date":"1991","source":"Acta tropica","url":"https://pubmed.ncbi.nlm.nih.gov/1684263","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GBP130"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"8303938","id":"PMC_8303938","title":"Immunogenicity and antigenicity of a Plasmodium falciparum protein fraction (90-110 kDa) able to protect squirrel monkeys against asexual blood stages.","date":"1994","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/8303938","citation_count":26,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GBP130"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"3298526","id":"PMC_3298526","title":"Possible pitfalls in the identification of glycophorin-binding proteins of Plasmodium falciparum.","date":"1987","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/3298526","citation_count":20,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11269326","id":"PMC_11269326","title":"Differences in nucleosome organization over episomally located plasmids coincides with aberrant promoter activity in P. falciparum.","date":"1999","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/11269326","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GBP130"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2404782","id":"PMC_2404782","title":"Chemical crosslinking of Plasmodium falciparum glycoprotein, Pf200 (190-205 kDa), to the S-antigen at the merozoite surface.","date":"1990","source":"Experimental 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America","url":"https://pubmed.ncbi.nlm.nih.gov/42695673","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfGBP130"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10747,"output_tokens":3777,"usd":0.044448,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9828,"output_tokens":4362,"usd":0.079095,"stage2_stop_reason":"end_turn"},"total_usd":0.123543,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1984,\n      \"finding\": \"GBP130 (130 kDa protein) is located on the merozoite surface coat and binds to glycophorin (erythrocyte sialoglycoprotein) in a saturable manner; antibodies against it inhibit merozoite invasion into erythrocytes and inhibit binding of the protein to a glycophorin-matrix.\",\n      \"method\": \"Glycophorin-coupled acrylamide matrix affinity binding assay, immunoelectron microscopy, invasion inhibition assay\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assay and invasion inhibition with antibodies, immunoelectron microscopy for localization, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"6206188\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1985,\n      \"finding\": \"The GBP130 gene was cloned and the primary sequence reveals a 150-nucleotide tandem-repeating sequence coding for a 50-amino-acid repeat; recombinant protein expressing these repeats interacts with glycophorin.\",\n      \"method\": \"cDNA cloning and sequencing, recombinant protein expression in E. coli, binding assay\",\n      \"journal\": \"Science (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gene cloning with sequence characterization and recombinant binding assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"3883491\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1986,\n      \"finding\": \"The glycophorin-binding domain of GBP130 resides in the tandemly repeated 50-amino-acid sequence (11 highly conserved copies); binding to glycophorin correlates with repeat number, and antibodies directed against the repeat sequence inhibit in vitro erythrocyte invasion by merozoites.\",\n      \"method\": \"Gene cloning and sequencing, recombinant protein expression of varying repeat numbers, glycophorin-binding assay, invasion inhibition with repeat-specific antibodies\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — recombinant domain mapping with mutagenesis-equivalent repeat-number variation, direct binding assay, functional antibody inhibition; replicated by independent cloning study (PMID 3883491)\",\n      \"pmids\": [\"3512098\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1987,\n      \"finding\": \"The glycophorin-binding specificity of GBP130 (and other proteins identified via glycophorin-coupled AE-BioGel) requires re-evaluation because the AE-BioGel matrix itself has strong ion-exchange properties that cause non-specific protein binding; this is a negative/cautionary result calling into question the specificity of the glycophorin-binding assay used to characterize GBP130.\",\n      \"method\": \"Glycophorin-coupled AE-BioGel binding assay with and without coupled glycophorin under varying ionic conditions\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct experimental demonstration of matrix artifact, single lab but mechanistically informative negative result\",\n      \"pmids\": [\"3298526\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1989,\n      \"finding\": \"GBP130 is accessible at the merozoite surface and is recognized by antibodies that inhibit merozoite dispersal from infected erythrocytes, as identified by probing 2D immunoblots with antibodies dissociated from immune complexes at the merozoite surface.\",\n      \"method\": \"Two-dimensional immunoblotting, antibody dissociation from immune complexes at merozoite surface\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct identification of surface-accessible antigen by antibody dissociation from immune complexes, single lab\",\n      \"pmids\": [\"2509909\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1990,\n      \"finding\": \"GBP130 was NOT detected in crosslinked immune complexes with the major merozoite surface glycoprotein Pf200, indicating GBP130 does not form a stable proximal complex with Pf200 at the merozoite surface under these conditions.\",\n      \"method\": \"Chemical crosslinking with dithiobis(succinimidyl) propionate, immunoprecipitation, immunoblotting\",\n      \"journal\": \"Experimental parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method; negative result (GBP130 not detected in Pf200 crosslinked complexes)\",\n      \"pmids\": [\"2404782\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1992,\n      \"finding\": \"The GBP130 gene resides within a cluster of three erythrocytic-stage transcription units on chromosome 10; nuclear run-on data demonstrate that transcription of GBP130 and its upstream neighbor is monocistronic despite being separated by less than 2 kb, with termination of the upstream gene and initiation of GBP130 occurring within this intergenic region.\",\n      \"method\": \"Yeast artificial chromosome (YAC) mapping, nuclear run-on transcription assay\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — nuclear run-on directly demonstrates monocistronic transcription and maps initiation/termination sites; single lab with two orthogonal methods\",\n      \"pmids\": [\"1374714\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"A discrete five base pair cis-acting sequence element within the GBP130 promoter is necessary for efficient promoter activity and binds nuclear factors in a sequence-specific manner; this element shares no homology with known eukaryotic transcription factor binding sites.\",\n      \"method\": \"Mutational analysis of promoter by deletion/substitution, reporter gene assay, electrophoretic mobility shift assay (EMSA) for nuclear factor binding\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — promoter mutagenesis combined with nuclear factor binding assay, single lab with two orthogonal methods\",\n      \"pmids\": [\"10215026\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"The GBP130 promoter loses its developmental (stage-specific) restriction and becomes constitutively active when placed on an episomal plasmid, coinciding with the absence of phased nucleosomal arrays over the episome, suggesting epigenetic (chromatin) regulation underlies the developmental control of GBP130 transcription.\",\n      \"method\": \"Transient transfection with episomal constructs, comparison with endogenous chromosomal promoter activity, nucleosome positioning analysis\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct comparison of episomal vs. chromosomal promoter activity linked to nucleosome organization, single lab with two orthogonal methods\",\n      \"pmids\": [\"11269326\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The length of the 5' UTR of GBP130 regulates promoter activity in a stage-specific manner: a shorter 5' UTR is functional at ring stage, while a longer 5' UTR promotes transcription at trophozoite and schizont stages; poly(dA:dT) tracts in the proximal sequence enhance promoter strength.\",\n      \"method\": \"Promoter deletion constructs transfected into P. falciparum, CAT reporter gene expression measured by liquid scintillation counting at defined developmental stages\",\n      \"journal\": \"Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single reporter method, limited controls described in abstract\",\n      \"pmids\": [\"12567560\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The P. falciparum TATA-binding protein (PfTBP) associates with a TATA box-like sequence (TGTAA) at position -186 of the GBP130 gene promoter region in vitro and in vivo, as shown by supershift, DNase I footprinting with GST-PfTBP fusion protein, and chromatin immunoprecipitation.\",\n      \"method\": \"EMSA supershift assay, DNase I footprinting with GST-PfTBP fusion protein, chromatin immunoprecipitation (ChIP)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — three orthogonal methods (EMSA, footprinting, ChIP) in a single lab demonstrating PfTBP binding to GBP130 promoter\",\n      \"pmids\": [\"15760658\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The extended N-terminal region of the GBP130 signal peptide is not required for directing the protein into the secretory pathway; multiple deletions of this N-terminal extension do not impair targeting of a fluorescent reporter to the secretory pathway, and the extension does not affect transport of soluble or membrane proteins to their correct subcellular localizations.\",\n      \"method\": \"Signal peptide deletion mutagenesis fused to fluorescent reporter, live-cell imaging of secretory pathway targeting in P. falciparum and mammalian cells\",\n      \"journal\": \"International journal of medical microbiology : IJMM\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct mutagenesis of signal peptide with functional reporter assay in P. falciparum and mammalian cells; single lab, multiple constructs and cell systems\",\n      \"pmids\": [\"28750796\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Antibodies targeting the GBP130-A region (aa 111-374) inhibit RBC invasion by P. falciparum in vitro when induced by mRNA or DNA immunogens, identifying this region as functionally important for invasion.\",\n      \"method\": \"Mouse immunization with lipid-encapsulated mRNA, DNA plasmid, and recombinant protein immunogens; in vitro growth inhibition/invasion inhibition assay\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro invasion inhibition assay with antisera against defined protein region; single lab with multiple immunogen formats\",\n      \"pmids\": [\"38863702\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"GBP130 is expressed on the surface of P. falciparum-infected RBCs and directly binds the I-domain of LFA-1 (LFA-1 αI); it was identified as a high-confidence LFA-1 ligand by LC-MS/MS analysis of LFA-1 αI-Fc immunoprecipitates from iRBCs, and recombinant GBP130 binds NK and THP-1 cells in an LFA-1-dependent manner, promoting NK cell activation, degranulation, and contact-dependent killing of iRBCs.\",\n      \"method\": \"LFA-1 αI-Fc fusion protein pulldown, LC-MS/MS proteomics, recombinant protein binding assay, NK cell co-culture activation/degranulation assay, neutralizing antibody inhibition of NK killing\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (affinity pulldown + mass spectrometry identification + recombinant binding assay + functional co-culture assay + antibody neutralization) in a single study establishing GBP130 as the LFA-1 ligand on iRBCs\",\n      \"pmids\": [\"42206825\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"GBP130 (PF3D7_1016300) is a P. falciparum merozoite surface protein whose tandemly repeated 50-amino-acid domain mediates binding to the erythrocyte receptor glycophorin in a repeat-number-dependent manner, facilitating RBC invasion; it is also expressed on the surface of infected RBCs where it serves as a ligand for the integrin LFA-1 on NK cells, promoting NK cell activation and parasite killing; its expression is regulated by a five-base-pair promoter element and phased nucleosomal arrays, with PfTBP binding a TATA box-like element in its promoter, and its extended signal peptide N-terminal region is dispensable for secretory pathway entry.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GBP130 (PF3D7_1016300) is a Plasmodium falciparum blood-stage protein that operates at the interface between the parasite and host erythrocytes and immune cells [#0, #13]. During merozoite invasion it localizes to the merozoite surface coat and binds the erythrocyte sialoglycoprotein glycophorin in a saturable manner; antibodies against it block both glycophorin binding and invasion [#0]. Its glycophorin-binding activity is carried by a tandemly repeated 50-amino-acid sequence, and binding scales with the number of repeats, while repeat-specific antibodies inhibit erythrocyte invasion [#1, #2]; antibodies against a defined N-terminal region (aa 111-374) likewise inhibit invasion [#12]. Transcription of GBP130 is developmentally controlled through cis-regulatory architecture on chromosome 10, including a five-base-pair promoter element that binds sequence-specific nuclear factors and a TATA box-like element bound by the P. falciparum TATA-binding protein PfTBP, with stage restriction linked to phased nucleosomal arrays over the endogenous locus [#7, #10, #8]. Beyond its invasion role, GBP130 is displayed on the surface of infected RBCs, where it directly binds the I-domain of the integrin LFA-1 and drives LFA-1-dependent NK cell activation, degranulation, and contact-dependent killing of infected erythrocytes [#13]. An early cautionary study showed the glycophorin-coupled AE-BioGel matrix used to define binding has intrinsic ion-exchange properties that can produce non-specific binding, qualifying the affinity-matrix data [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 1984,\n      \"claim\": \"Established that GBP130 is a merozoite-surface protein with a defined host-receptor binding activity, raising the possibility that it participates in erythrocyte invasion.\",\n      \"evidence\": \"Glycophorin-matrix affinity binding, immunoelectron microscopy, and antibody invasion-inhibition in P. falciparum\",\n      \"pmids\": [\"6206188\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Affinity-matrix binding later shown to be subject to non-specific artifact\", \"No mapping of the binding domain at this stage\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1986,\n      \"claim\": \"Localized the glycophorin-binding function to a tandem 50-amino-acid repeat and showed binding depends on repeat number, defining the molecular basis of receptor engagement and its inhibition.\",\n      \"evidence\": \"cDNA cloning/sequencing and recombinant expression of variable repeat numbers with glycophorin binding and repeat-specific antibody invasion inhibition in P. falciparum\",\n      \"pmids\": [\"3883491\", \"3512098\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of repeat-glycophorin interaction unresolved\", \"Contribution of non-repeat regions to invasion not defined here\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1987,\n      \"claim\": \"Questioned the specificity of the primary assay used to characterize GBP130 binding by showing the affinity matrix itself binds proteins non-specifically.\",\n      \"evidence\": \"Glycophorin-coupled AE-BioGel binding assay with and without glycophorin under varying ionic conditions in P. falciparum\",\n      \"pmids\": [\"3298526\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not overturn the antibody-based invasion inhibition data\", \"Extent of artifact for GBP130 specifically not quantified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1990,\n      \"claim\": \"Tested whether GBP130 physically partners with the major merozoite surface glycoprotein Pf200 and found no stable proximal complex under crosslinking conditions.\",\n      \"evidence\": \"Chemical crosslinking, immunoprecipitation, and immunoblotting in P. falciparum\",\n      \"pmids\": [\"2404782\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single method negative result; absence of crosslinking does not exclude transient association\", \"No reciprocal or alternative interaction screen\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1992,\n      \"claim\": \"Defined the genomic and transcriptional context of GBP130, showing it is monocistronically transcribed within a chromosome-10 gene cluster.\",\n      \"evidence\": \"YAC mapping and nuclear run-on transcription assay in P. falciparum\",\n      \"pmids\": [\"1374714\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Regulatory elements not yet identified\", \"Functional consequence of the clustered arrangement unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Identified cis-regulatory and chromatin determinants of GBP130 expression, linking developmental stage restriction to a discrete promoter element and to phased nucleosomal arrays.\",\n      \"evidence\": \"Promoter mutagenesis with reporter assays and EMSA, plus episomal vs chromosomal promoter comparison with nucleosome positioning in P. falciparum\",\n      \"pmids\": [\"10215026\", \"11269326\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identity of the sequence-specific nuclear factor not determined\", \"Mechanistic link between nucleosome phasing and stage timing not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Proposed that 5' UTR length and poly(dA:dT) tracts tune stage-specific promoter output for GBP130.\",\n      \"evidence\": \"Promoter/5' UTR deletion CAT reporter constructs at defined developmental stages in P. falciparum\",\n      \"pmids\": [\"12567560\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single reporter method with limited controls\", \"Endogenous relevance of 5' UTR length variation not confirmed\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Placed GBP130 transcription within basal machinery by demonstrating PfTBP binding to a TATA box-like element in its promoter.\",\n      \"evidence\": \"EMSA supershift, DNase I footprinting with GST-PfTBP, and ChIP in P. falciparum\",\n      \"pmids\": [\"15760658\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional requirement of PfTBP occupancy for GBP130 expression not tested\", \"Interplay with the five-base-pair element unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Dissected the unusually extended signal peptide and showed its N-terminal extension is dispensable for secretory-pathway entry.\",\n      \"evidence\": \"Signal peptide deletion mutagenesis fused to fluorescent reporters imaged in P. falciparum and mammalian cells\",\n      \"pmids\": [\"28750796\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Alternative function of the extended N-terminus not identified\", \"No effect on trafficking of native full-length GBP130 tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified a discrete invasion-relevant epitope region (aa 111-374) whose antibodies block invasion, supporting GBP130 as a vaccine-relevant invasion antigen.\",\n      \"evidence\": \"Mouse immunization with mRNA, DNA, and recombinant protein immunogens and in vitro growth/invasion inhibition assays for P. falciparum\",\n      \"pmids\": [\"38863702\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of inhibition by this region not defined\", \"Receptor engaged by the aa 111-374 region not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Revealed a second, immune-facing role for GBP130 as an infected-RBC surface ligand for the LFA-1 integrin that triggers NK-cell killing of infected erythrocytes.\",\n      \"evidence\": \"LFA-1 alphaI-Fc pulldown with LC-MS/MS, recombinant binding assays, and NK/THP-1 co-culture activation, degranulation and neutralization assays with P. falciparum iRBCs\",\n      \"pmids\": [\"42206825\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of GBP130-LFA-1 alphaI binding not resolved\", \"How merozoite-surface GBP130 relates to iRBC-surface display not established\", \"In vivo relevance of NK-mediated killing not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how GBP130's two receptor engagements (glycophorin during invasion versus LFA-1 on the infected-RBC surface) are structurally and temporally coordinated, and whether the tandem repeat and the aa 111-374 region contribute to each function.\",\n      \"evidence\": \"No timeline discovery integrates the invasion and immune-ligand roles or provides a structural model\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of any GBP130 domain\", \"No genetic knockout/knockdown phenotype in the corpus\", \"Domain assignment for LFA-1 binding not mapped\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005102\", \"supporting_discovery_ids\": [0, 1, 2, 13]},\n      {\"term_id\": \"GO:0050839\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"GO:0043621\", \"supporting_discovery_ids\": [7, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0020030\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0, 2, 12]},\n      {\"term_id\": \"GO:0042267\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"GO:0006355\", \"supporting_discovery_ids\": [7, 8, 9, 10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"glycophorin (erythrocyte sialoglycoprotein) [#0, #1, #2]\",\n      \"LFA-1 integrin (alphaI/I-domain) [#13]\",\n      \"PfTBP (P. falciparum TATA-binding protein) [#10]\"\n    ],\n    \"other_free_text\": [\n      \"Glycophorin-binding activity maps to a tandem 50-amino-acid repeat (11 conserved copies) and scales with repeat number [#2, #1].\",\n      \"aa 111-374 region antibodies inhibit invasion, marking it as functionally important [#12].\",\n      \"Extended N-terminal signal-peptide region is dispensable for secretory-pathway entry [#11].\",\n      \"GBP130 was not detected in crosslinked complexes with the major surface glycoprotein Pf200 [#5].\",\n      \"Early glycophorin affinity-matrix data are qualified by an ion-exchange artifact of the AE-BioGel matrix [#3].\",\n      \"Gene lies in a chromosome-10 cluster and is transcribed monocistronically; developmental control is linked to phased nucleosomal arrays and a five-base-pair promoter element [#6, #7, #8].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1016300","name":null,"product":"GBP130 protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"GBP130","evaluation":null}