{"gene":"PF3D7_0309600","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2012,"finding":"PfP2 is exported to the infected erythrocyte (IE) surface during early schizogony (26–28 hrs post-merozoite invasion) as SDS-resistant homo-tetramers, and treatment with anti-PfP2 monoclonal antibodies arrests IEs at the first nuclear division; upon antibody removal, ~80–85% of parasites resume division. Anti-PfP2 antibodies also cause complete fragmentation of the tubovesicular network (TVN) and impair lipid import, identified as downstream causes of cell-cycle arrest.","method":"PfP2-GFP transfection, multiple PfP2-specific monoclonal antibodies (surface blocking), synchronized parasite culture, TVN imaging, lipid import assay","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (GFP transfection, monoclonal antibody blocking, TVN/lipid import assays) with reversibility controls; replicated in P. yoelii and P. berghei","pmids":["22912579"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium yoelii","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2012,"finding":"Recombinant PfP2 undergoes SDS-resistant oligomerization that is significantly reduced under reducing conditions, but continues even when both cysteine residues are mutated and up to 40 C-terminal amino acids are deleted, indicating multiple structural determinants for oligomerization. In synchronized P. falciparum cultures, PfP2 is part of the ribosomal complex (~96 kDa) at 18 and 30 hrs post-merozoite invasion (PMI) in an SDS-sensitive form, but at 30 hrs large SDS-sensitive aggregates >600 kDa also appear; parasite extracts from 24–36 hrs PMI specifically induce DTT- and SDS-resistant oligomerization of labeled recombinant PfP2, requiring multiple parasite proteins.","method":"SDS-PAGE of cysteine and C-terminal deletion mutants, CD spectroscopy, TMR-labeled rPfP2 incubation with stage-specific parasite extracts, synchronized erythrocytic culture fractionation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (mutagenesis, CD, stage-specific extract incubation, fractionation) in a single focused study","pmids":["23060439"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"NMR studies of recombinant PfP2 show the protein is largely helical but undergoes extensive self-association; only 43 of the expected 138 1H-15N HSQC cross-peaks are observed for native PfP2, and the observable peaks map to the flexible, solvent-exposed C-terminal region. Under denaturing conditions (9 M urea), the chain shows predominantly non-native β-structural propensity, and 15N relaxation data reveal ms–µs timescale motion variation along the chain coinciding with hydrophobic patches, suggesting transient hydrophobic collapse drives self-association.","method":"NMR (1H-15N HSQC, 15N relaxation), circular dichroism, light scattering, SDS-PAGE of recombinant PfP2","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — structural NMR with multiple biophysical corroboration, single lab","pmids":["22567147"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"NMR dissociation-association experiments mapped the nucleation site for PfP2 self-association to residues Met31–Leu44 (corresponding to Met1–Leu14 of the mature protein), with further association driven by hydrophobic and complementary electrostatic interactions; residues Ile97–Ala116 remain persistently flexible and may serve as a hinge for segmental motion. In-cell HSQC spectra in E. coli closely matched in vitro spectra, confirming that PfP2 has similar intrinsic aggregation tendencies in vivo and in vitro.","method":"In vitro and in-cell NMR (HSQC), 15N relaxation, dissociation-association strategy with recombinant PfP2","journal":"Journal of biomolecular structure & dynamics","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — NMR-based residue-level mapping with in-cell validation, single lab","pmids":["23581826"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"PfP2 forms a stable homo-tetramer (two dimers associating sideways with close packing of helices at the interface) that retains a molten globule character: PfP2 forms a molten globule monomer at low pH, and at physiological pH and micromolar concentrations exists as a stable tetramer. The molten globule characteristic of the monomer is preserved in the tetramer.","method":"NMR spectral characteristics and 15N relaxation dispersion under varied pH and urea; circular dichroism; multiple biophysical techniques","journal":"Biochemistry and biophysics reports","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — structural NMR with multiple biophysical methods, single lab","pmids":["29124138"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"PfP2 localizes to the surface of P. falciparum merozoites, and antibodies raised against PfP2 block merozoite invasion of host cells.","method":"Immunofluorescence/surface detection with P2-specific antibodies; invasion inhibition assay","journal":"Parasitology international","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — antibody-based surface detection and functional invasion inhibition assay, single lab","pmids":["25280460"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"The P. falciparum ribosomal stalk assembles as a pentamer (uL10/P0–(P1–P2)₂) through a unique one-step trilateral interaction requiring all three proteins (P0, P1, PfP2) simultaneously; no stable P1–PfP2 heterodimeric intermediate exists. The PfP2 homo-oligomer is proposed as an off-pathway product with physiologically important non-ribosomal roles.","method":"Tricistronic bacterial expression of P. falciparum P-stalk complex, bacterial two-hybrid assay, mass spectrometry, biochemical and biophysical analyses","journal":"Biochimica et biophysica acta","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vivo reconstitution in bacterial system plus mass spectrometry, two-hybrid, and biophysical corroboration; single lab but multiple orthogonal methods","pmids":["25450178"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"The C-terminal ~50 amino acid domain of PfP2 is intrinsically disordered: CD shows no stable secondary structures, and 1H-15N HSQC spectra show rapid monomer-multimer equilibrium with narrow spectral dispersion, revealing short segments with preferred secondary structural propensities at conserved positions.","method":"Gel filtration, circular dichroism, NMR (1H-15N HSQC) of expressed C-terminal domain of PfP2","journal":"Protein and peptide letters","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — structural NMR and CD of isolated domain, single lab","pmids":["25412900"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"The C-terminal ~45 residues of PfP2 behave as an independent intrinsically disordered peptide: 15N NMR relaxation parameters and derived rotational correlation times for this segment are essentially invariant across different urea concentrations that produce different mixtures of PfP2 oligomers, while the remainder of the protein shows substantial variation, indicating the C-terminal domain remains flexibly disordered regardless of oligomeric state.","method":"15N NMR relaxation measurements at varying urea concentrations on PfP2 multimers","journal":"Protein and peptide letters","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — quantitative NMR relaxation under multiple conditions, single lab","pmids":["25747872"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"The homo-tetrameric form of PfP2 binds specifically to erythrocytes but not leukocytes; the hydrophobic N-terminal 72 amino acid region is the major interacting domain. Binding is neuraminidase-resistant but trypsin-sensitive. Pull-down, immunoprecipitation, and mass spectrometry identified erythrocytic Band 3 protein as a binding partner of PfP2 on the erythrocyte surface. The homologous TgP2 protein did not interact with erythrocytes.","method":"NMR binding studies, erythrocyte pull-down assay, immunoprecipitation, mass spectrometry, neuraminidase/trypsin treatment","journal":"Biochimie","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (NMR, pull-down, IP, MS), identification of specific binding partner (Band 3), single lab","pmids":["32717409"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"At the onset of schizogony, the IE surface-exposed denaturation-resistant PfP2 tetramer imports serum fatty acids (FAs) into the parasite; blockage of this import reversibly arrests parasite schizogony. The denaturation resistance of the tetramer is mediated by Met11–O–Met11 (methionine oxidation) linkages, and a Cys12/Cys53 disulfide redox switch regulates binding and release of FAs based on the oxidized/reduced state of disulfide linkages.","method":"FA import assays with synchronized P. falciparum, reversible blockage experiments, biochemical characterization of Met-O-Met and Cys-Cys redox states","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional FA import assay with reversibility, redox state characterization, single lab","pmids":["38726364"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfP2 (PF3D7_0309600) is a 60S ribosomal stalk protein that assembles into the canonical pentameric P-stalk (uL10/P0–(P1–PfP2)₂) via a unique one-step trilateral interaction with no stable P1–PfP2 intermediate; additionally, during early schizogony it is exported to the infected erythrocyte surface as a denaturation-resistant homo-tetramer—stabilized by Met11-O-Met11 linkages and regulated by a Cys12/Cys53 redox switch—where it anchors to Band 3 via its hydrophobic N-terminal domain and imports serum fatty acids required for nuclear division, such that antibody blockade or import inhibition reversibly arrests the first nuclear division."},"narrative":{"mechanistic_narrative":"PfP2 (PF3D7_0309600) is a 60S acidic ribosomal stalk protein of Plasmodium falciparum that additionally performs a moonlighting role at the infected-erythrocyte surface during schizogony [PMID:22912579, PMID:25450178]. As a ribosomal component, PfP2 assembles into the pentameric P-stalk (uL10/P0–(P1–PfP2)₂) through a unique one-step trilateral interaction that requires P0, P1, and PfP2 simultaneously, with no stable P1–PfP2 heterodimeric intermediate; its homo-oligomer is an off-pathway species proposed to carry the non-ribosomal functions [PMID:25450178]. In its non-ribosomal role, PfP2 is exported to the infected-erythrocyte surface as SDS-resistant homo-tetramers during early schizogony (26–28 h post-invasion), where blocking it with monoclonal antibodies reversibly arrests parasites at the first nuclear division, fragments the tubovesicular network, and impairs lipid import [PMID:22912579]. The exported tetramer anchors to erythrocytic Band 3 via its hydrophobic N-terminal region and imports serum fatty acids required for schizogony, with a Met11–O–Met11 oxidation linkage conferring denaturation resistance and a Cys12/Cys53 redox switch governing fatty-acid binding and release [PMID:32717409, PMID:38726364]. Biophysically, PfP2 is largely helical yet strongly self-associating, forming a molten-globule tetramer nucleated at its N-terminal Met1–Leu14 hydrophobic segment while its C-terminal ~45–50 residues remain intrinsically disordered independent of oligomeric state [PMID:23581826, PMID:29124138, PMID:25412900]. PfP2 also localizes to the merozoite surface, where anti-PfP2 antibodies block host-cell invasion [PMID:25280460].","teleology":[{"year":2012,"claim":"Establishing that a ribosomal stalk protein has an extra-ribosomal, surface-exposed function answered whether PfP2 acts beyond translation, linking it directly to the parasite cell cycle.","evidence":"PfP2-GFP transfection plus surface-blocking monoclonal antibodies with reversibility controls, TVN imaging and lipid-import assays in synchronized P. falciparum, P. yoelii and P. berghei","pmids":["22912579"],"confidence":"High","gaps":["Export machinery routing PfP2 to the IE surface not identified","Molecular link between surface PfP2 and nuclear-division control not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium yoelii","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2012,"claim":"Characterizing the biochemical basis of PfP2 oligomerization addressed whether a single motif drives the SDS-resistant tetramer and whether parasite factors are required, revealing multiple determinants and a stage-specific inducing activity.","evidence":"SDS-PAGE of cysteine and C-terminal deletion mutants, CD spectroscopy, and TMR-labeled recombinant PfP2 incubated with stage-specific parasite extracts","pmids":["23060439"],"confidence":"High","gaps":["Identity of the parasite proteins inducing DTT/SDS-resistant oligomerization not determined","Relationship between the >600 kDa aggregates and functional tetramer unclear"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Residue-level NMR mapping answered where self-association nucleates, pinpointing an N-terminal hydrophobic segment and a persistently flexible internal hinge.","evidence":"In vitro and in-cell NMR HSQC, 15N relaxation, and dissociation-association strategy with recombinant PfP2 in E. coli","pmids":["23581826"],"confidence":"Medium","gaps":["High-resolution structure of the oligomer interface absent","In-cell relevance to parasite tetramer not directly tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Defining the tetramer as a molten-globule assembly clarified the unusual physical state of the functional oligomer at physiological pH.","evidence":"NMR spectral characteristics and 15N relaxation dispersion across pH and urea, with CD and additional biophysical methods on recombinant PfP2","pmids":["29124138"],"confidence":"Medium","gaps":["Functional consequence of molten-globule character in vivo untested","No atomic structure of the tetramer"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Reconstituting the P-stalk answered how PfP2 integrates into the ribosome, revealing a one-step trilateral assembly and framing the homo-oligomer as an off-pathway, functionally distinct species.","evidence":"Tricistronic bacterial expression of the P. falciparum P-stalk, bacterial two-hybrid, mass spectrometry, and biophysical analyses","pmids":["25450178"],"confidence":"High","gaps":["Stoichiometric partitioning between ribosomal and off-pathway pools in the parasite unknown","Trigger diverting PfP2 to the non-ribosomal pathway not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Detecting PfP2 on the merozoite surface and blocking invasion with anti-PfP2 antibodies extended its extra-ribosomal role to a second cell-cycle stage.","evidence":"P2-specific antibody surface detection and invasion-inhibition assay in P. falciparum","pmids":["25280460"],"confidence":"Medium","gaps":["Merozoite-surface binding partner not identified","Mechanism by which surface PfP2 contributes to invasion unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Characterizing the C-terminal domain established that it is intrinsically disordered independent of oligomeric state, separating the folded self-associating core from the flexible tail.","evidence":"Gel filtration, CD, and NMR HSQC of the isolated C-terminal domain, plus 15N relaxation across urea concentrations","pmids":["25412900","25747872"],"confidence":"Medium","gaps":["Functional role of the disordered C-terminus in ribosomal or surface activity not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Identifying Band 3 as the erythrocyte receptor answered how surface PfP2 anchors to the host membrane and localized the interaction to the hydrophobic N-terminal domain.","evidence":"NMR binding studies, erythrocyte pull-down, immunoprecipitation, mass spectrometry, and neuraminidase/trypsin treatment; TgP2 negative control","pmids":["32717409"],"confidence":"High","gaps":["Binding stoichiometry and affinity to Band 3 not quantified","Whether Band 3 binding is required for fatty-acid import not directly tested here"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Linking the surface tetramer to serum fatty-acid import and defining a Met-oxidation stabilization plus Cys12/Cys53 redox switch answered how PfP2 physically supports schizogony.","evidence":"Fatty-acid import assays with reversible blockage in synchronized P. falciparum and biochemical characterization of Met-O-Met and Cys-Cys redox states","pmids":["38726364"],"confidence":"Medium","gaps":["Transport mechanism moving fatty acids from surface PfP2 into the parasite unresolved","Enzymes controlling the Met oxidation and disulfide redox states not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How the parasite partitions PfP2 between its ribosomal P-stalk role and its exported surface fatty-acid-import role, and what machinery exports and modifies it, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Export pathway to the IE surface unknown","Regulatory trigger for off-pathway homo-tetramer formation undefined","Enzymes controlling Met-O-Met and Cys redox modifications unidentified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["60S ribosomal P-stalk pentamer uL10/P0–(P1–PfP2)₂ [#6]","PfP2 homo-tetramer (off-pathway, surface-exported) [#0, #4]"],"partners":["P0 (UL10) RIBOSOMAL STALK PROTEIN [#6]","P1 RIBOSOMAL STALK PROTEIN [#6]","ERYTHROCYTIC BAND 3 [#9]"],"other_free_text":["SDS/denaturation-resistant homo-tetramer exported to the infected-erythrocyte surface at 26–28 h post-invasion; anti-PfP2 antibody blockade reversibly arrests first nuclear division and fragments the tubovesicular network [#0]","Self-association nucleates at the N-terminal Met1–Leu14 hydrophobic segment; C-terminal ~45–50 residues are intrinsically disordered regardless of oligomeric state [#3, #7, #8]","Tetramer retains molten-globule character at physiological pH [#4]","Denaturation resistance mediated by Met11–O–Met11 linkages; Cys12/Cys53 disulfide redox switch controls fatty-acid binding and release [#10]","Erythrocyte binding is neuraminidase-resistant but trypsin-sensitive; the homologous TgP2 does not bind erythrocytes [#9]","Localizes to the merozoite surface; anti-PfP2 antibodies inhibit invasion [#5]","Stage-specific parasite extracts (24–36 h post-invasion) induce DTT/SDS-resistant oligomerization of recombinant PfP2, requiring multiple parasite proteins [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"22912579","id":"PMC_22912579","title":"Arrest of nuclear division in Plasmodium through blockage of erythrocyte surface exposed ribosomal protein P2.","date":"2012","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/22912579","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PFC0400w","PfP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22567147","id":"PMC_22567147","title":"NMR insights into folding and self-association of Plasmodium falciparum P2.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22567147","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25280460","id":"PMC_25280460","title":"Ribosomal protein P2 localizes to the parasite zoite-surface and is a target for invasion inhibitory antibodies in Toxoplasma gondii and Plasmodium falciparum.","date":"2014","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/25280460","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfP2"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":false},{"pmid":"23060439","id":"PMC_23060439","title":"Erythrocytic stage-dependent regulation of oligomerization of Plasmodium ribosomal protein P2.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23060439","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9603498","id":"PMC_9603498","title":"Plasmodium falciparum: ribosomal P2 protein gene expression is independent of the developmentally regulated rRNAs.","date":"1998","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/9603498","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23581826","id":"PMC_23581826","title":"Residue level description of in vivo self-association of Plasmodium falciparum P2.","date":"2013","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/23581826","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29124138","id":"PMC_29124138","title":"Molten globule nature of Plasmodium falciparum P2 homo-tetramer.","date":"2015","source":"Biochemistry and biophysics reports","url":"https://pubmed.ncbi.nlm.nih.gov/29124138","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38759952","id":"PMC_38759952","title":"Proteomes of plasmodium knowlesi early and late ring-stage parasites and infected host erythrocytes.","date":"2024","source":"Journal of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/38759952","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["60S acidic ribosomal protein P2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32717409","id":"PMC_32717409","title":"Molecular study of binding of Plasmodium ribosomal protein P2 to erythrocytes.","date":"2020","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/32717409","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25412900","id":"PMC_25412900","title":"The C-terminal domain of eukaryotic acidic ribosomal P2 proteins is intrinsically disordered with conserved structural propensities.","date":"2014","source":"Protein and peptide letters","url":"https://pubmed.ncbi.nlm.nih.gov/25412900","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25450178","id":"PMC_25450178","title":"In vivo formation of Plasmodium falciparum ribosomal stalk - a unique mode of assembly without stable heterodimeric intermediates.","date":"2014","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/25450178","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25747872","id":"PMC_25747872","title":"Urea Dependent (15)N NMR-Relaxation Studies on PfP2 Multimers Reveal that the C-Terminal Behaves like an Independent Intrinsically Disordered Peptide.","date":"2015","source":"Protein and peptide letters","url":"https://pubmed.ncbi.nlm.nih.gov/25747872","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38726364","id":"PMC_38726364","title":"M-O-M mediated denaturation resistant P2 tetramer on the infected erythrocyte surface of malaria parasite imports serum fatty acids.","date":"2024","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/38726364","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9485,"output_tokens":3486,"usd":0.040372,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9291,"output_tokens":4298,"usd":0.076952,"stage2_stop_reason":"end_turn"},"total_usd":0.117324,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"PfP2 is exported to the infected erythrocyte (IE) surface during early schizogony (26–28 hrs post-merozoite invasion) as SDS-resistant homo-tetramers, and treatment with anti-PfP2 monoclonal antibodies arrests IEs at the first nuclear division; upon antibody removal, ~80–85% of parasites resume division. Anti-PfP2 antibodies also cause complete fragmentation of the tubovesicular network (TVN) and impair lipid import, identified as downstream causes of cell-cycle arrest.\",\n      \"method\": \"PfP2-GFP transfection, multiple PfP2-specific monoclonal antibodies (surface blocking), synchronized parasite culture, TVN imaging, lipid import assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (GFP transfection, monoclonal antibody blocking, TVN/lipid import assays) with reversibility controls; replicated in P. yoelii and P. berghei\",\n      \"pmids\": [\"22912579\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Recombinant PfP2 undergoes SDS-resistant oligomerization that is significantly reduced under reducing conditions, but continues even when both cysteine residues are mutated and up to 40 C-terminal amino acids are deleted, indicating multiple structural determinants for oligomerization. In synchronized P. falciparum cultures, PfP2 is part of the ribosomal complex (~96 kDa) at 18 and 30 hrs post-merozoite invasion (PMI) in an SDS-sensitive form, but at 30 hrs large SDS-sensitive aggregates >600 kDa also appear; parasite extracts from 24–36 hrs PMI specifically induce DTT- and SDS-resistant oligomerization of labeled recombinant PfP2, requiring multiple parasite proteins.\",\n      \"method\": \"SDS-PAGE of cysteine and C-terminal deletion mutants, CD spectroscopy, TMR-labeled rPfP2 incubation with stage-specific parasite extracts, synchronized erythrocytic culture fractionation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (mutagenesis, CD, stage-specific extract incubation, fractionation) in a single focused study\",\n      \"pmids\": [\"23060439\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"NMR studies of recombinant PfP2 show the protein is largely helical but undergoes extensive self-association; only 43 of the expected 138 1H-15N HSQC cross-peaks are observed for native PfP2, and the observable peaks map to the flexible, solvent-exposed C-terminal region. Under denaturing conditions (9 M urea), the chain shows predominantly non-native β-structural propensity, and 15N relaxation data reveal ms–µs timescale motion variation along the chain coinciding with hydrophobic patches, suggesting transient hydrophobic collapse drives self-association.\",\n      \"method\": \"NMR (1H-15N HSQC, 15N relaxation), circular dichroism, light scattering, SDS-PAGE of recombinant PfP2\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — structural NMR with multiple biophysical corroboration, single lab\",\n      \"pmids\": [\"22567147\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"NMR dissociation-association experiments mapped the nucleation site for PfP2 self-association to residues Met31–Leu44 (corresponding to Met1–Leu14 of the mature protein), with further association driven by hydrophobic and complementary electrostatic interactions; residues Ile97–Ala116 remain persistently flexible and may serve as a hinge for segmental motion. In-cell HSQC spectra in E. coli closely matched in vitro spectra, confirming that PfP2 has similar intrinsic aggregation tendencies in vivo and in vitro.\",\n      \"method\": \"In vitro and in-cell NMR (HSQC), 15N relaxation, dissociation-association strategy with recombinant PfP2\",\n      \"journal\": \"Journal of biomolecular structure & dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR-based residue-level mapping with in-cell validation, single lab\",\n      \"pmids\": [\"23581826\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PfP2 forms a stable homo-tetramer (two dimers associating sideways with close packing of helices at the interface) that retains a molten globule character: PfP2 forms a molten globule monomer at low pH, and at physiological pH and micromolar concentrations exists as a stable tetramer. The molten globule characteristic of the monomer is preserved in the tetramer.\",\n      \"method\": \"NMR spectral characteristics and 15N relaxation dispersion under varied pH and urea; circular dichroism; multiple biophysical techniques\",\n      \"journal\": \"Biochemistry and biophysics reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — structural NMR with multiple biophysical methods, single lab\",\n      \"pmids\": [\"29124138\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PfP2 localizes to the surface of P. falciparum merozoites, and antibodies raised against PfP2 block merozoite invasion of host cells.\",\n      \"method\": \"Immunofluorescence/surface detection with P2-specific antibodies; invasion inhibition assay\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — antibody-based surface detection and functional invasion inhibition assay, single lab\",\n      \"pmids\": [\"25280460\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The P. falciparum ribosomal stalk assembles as a pentamer (uL10/P0–(P1–P2)₂) through a unique one-step trilateral interaction requiring all three proteins (P0, P1, PfP2) simultaneously; no stable P1–PfP2 heterodimeric intermediate exists. The PfP2 homo-oligomer is proposed as an off-pathway product with physiologically important non-ribosomal roles.\",\n      \"method\": \"Tricistronic bacterial expression of P. falciparum P-stalk complex, bacterial two-hybrid assay, mass spectrometry, biochemical and biophysical analyses\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vivo reconstitution in bacterial system plus mass spectrometry, two-hybrid, and biophysical corroboration; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"25450178\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The C-terminal ~50 amino acid domain of PfP2 is intrinsically disordered: CD shows no stable secondary structures, and 1H-15N HSQC spectra show rapid monomer-multimer equilibrium with narrow spectral dispersion, revealing short segments with preferred secondary structural propensities at conserved positions.\",\n      \"method\": \"Gel filtration, circular dichroism, NMR (1H-15N HSQC) of expressed C-terminal domain of PfP2\",\n      \"journal\": \"Protein and peptide letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — structural NMR and CD of isolated domain, single lab\",\n      \"pmids\": [\"25412900\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The C-terminal ~45 residues of PfP2 behave as an independent intrinsically disordered peptide: 15N NMR relaxation parameters and derived rotational correlation times for this segment are essentially invariant across different urea concentrations that produce different mixtures of PfP2 oligomers, while the remainder of the protein shows substantial variation, indicating the C-terminal domain remains flexibly disordered regardless of oligomeric state.\",\n      \"method\": \"15N NMR relaxation measurements at varying urea concentrations on PfP2 multimers\",\n      \"journal\": \"Protein and peptide letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — quantitative NMR relaxation under multiple conditions, single lab\",\n      \"pmids\": [\"25747872\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The homo-tetrameric form of PfP2 binds specifically to erythrocytes but not leukocytes; the hydrophobic N-terminal 72 amino acid region is the major interacting domain. Binding is neuraminidase-resistant but trypsin-sensitive. Pull-down, immunoprecipitation, and mass spectrometry identified erythrocytic Band 3 protein as a binding partner of PfP2 on the erythrocyte surface. The homologous TgP2 protein did not interact with erythrocytes.\",\n      \"method\": \"NMR binding studies, erythrocyte pull-down assay, immunoprecipitation, mass spectrometry, neuraminidase/trypsin treatment\",\n      \"journal\": \"Biochimie\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (NMR, pull-down, IP, MS), identification of specific binding partner (Band 3), single lab\",\n      \"pmids\": [\"32717409\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"At the onset of schizogony, the IE surface-exposed denaturation-resistant PfP2 tetramer imports serum fatty acids (FAs) into the parasite; blockage of this import reversibly arrests parasite schizogony. The denaturation resistance of the tetramer is mediated by Met11–O–Met11 (methionine oxidation) linkages, and a Cys12/Cys53 disulfide redox switch regulates binding and release of FAs based on the oxidized/reduced state of disulfide linkages.\",\n      \"method\": \"FA import assays with synchronized P. falciparum, reversible blockage experiments, biochemical characterization of Met-O-Met and Cys-Cys redox states\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional FA import assay with reversibility, redox state characterization, single lab\",\n      \"pmids\": [\"38726364\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PfP2 (PF3D7_0309600) is a 60S ribosomal stalk protein that assembles into the canonical pentameric P-stalk (uL10/P0–(P1–PfP2)₂) via a unique one-step trilateral interaction with no stable P1–PfP2 intermediate; additionally, during early schizogony it is exported to the infected erythrocyte surface as a denaturation-resistant homo-tetramer—stabilized by Met11-O-Met11 linkages and regulated by a Cys12/Cys53 redox switch—where it anchors to Band 3 via its hydrophobic N-terminal domain and imports serum fatty acids required for nuclear division, such that antibody blockade or import inhibition reversibly arrests the first nuclear division.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PfP2 (PF3D7_0309600) is a 60S acidic ribosomal stalk protein of Plasmodium falciparum that additionally performs a moonlighting role at the infected-erythrocyte surface during schizogony [#0, #6]. As a ribosomal component, PfP2 assembles into the pentameric P-stalk (uL10/P0\\u2013(P1\\u2013PfP2)\\u2082) through a unique one-step trilateral interaction that requires P0, P1, and PfP2 simultaneously, with no stable P1\\u2013PfP2 heterodimeric intermediate; its homo-oligomer is an off-pathway species proposed to carry the non-ribosomal functions [#6]. In its non-ribosomal role, PfP2 is exported to the infected-erythrocyte surface as SDS-resistant homo-tetramers during early schizogony (26\\u201328 h post-invasion), where blocking it with monoclonal antibodies reversibly arrests parasites at the first nuclear division, fragments the tubovesicular network, and impairs lipid import [#0]. The exported tetramer anchors to erythrocytic Band 3 via its hydrophobic N-terminal region and imports serum fatty acids required for schizogony, with a Met11\\u2013O\\u2013Met11 oxidation linkage conferring denaturation resistance and a Cys12/Cys53 redox switch governing fatty-acid binding and release [#9, #10]. Biophysically, PfP2 is largely helical yet strongly self-associating, forming a molten-globule tetramer nucleated at its N-terminal Met1\\u2013Leu14 hydrophobic segment while its C-terminal ~45\\u201350 residues remain intrinsically disordered independent of oligomeric state [#3, #4, #7]. PfP2 also localizes to the merozoite surface, where anti-PfP2 antibodies block host-cell invasion [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing that a ribosomal stalk protein has an extra-ribosomal, surface-exposed function answered whether PfP2 acts beyond translation, linking it directly to the parasite cell cycle.\",\n      \"evidence\": \"PfP2-GFP transfection plus surface-blocking monoclonal antibodies with reversibility controls, TVN imaging and lipid-import assays in synchronized P. falciparum, P. yoelii and P. berghei\",\n      \"pmids\": [\"22912579\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Export machinery routing PfP2 to the IE surface not identified\", \"Molecular link between surface PfP2 and nuclear-division control not resolved\"],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Characterizing the biochemical basis of PfP2 oligomerization addressed whether a single motif drives the SDS-resistant tetramer and whether parasite factors are required, revealing multiple determinants and a stage-specific inducing activity.\",\n      \"evidence\": \"SDS-PAGE of cysteine and C-terminal deletion mutants, CD spectroscopy, and TMR-labeled recombinant PfP2 incubated with stage-specific parasite extracts\",\n      \"pmids\": [\"23060439\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the parasite proteins inducing DTT/SDS-resistant oligomerization not determined\", \"Relationship between the >600 kDa aggregates and functional tetramer unclear\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Residue-level NMR mapping answered where self-association nucleates, pinpointing an N-terminal hydrophobic segment and a persistently flexible internal hinge.\",\n      \"evidence\": \"In vitro and in-cell NMR HSQC, 15N relaxation, and dissociation-association strategy with recombinant PfP2 in E. coli\",\n      \"pmids\": [\"23581826\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"High-resolution structure of the oligomer interface absent\", \"In-cell relevance to parasite tetramer not directly tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defining the tetramer as a molten-globule assembly clarified the unusual physical state of the functional oligomer at physiological pH.\",\n      \"evidence\": \"NMR spectral characteristics and 15N relaxation dispersion across pH and urea, with CD and additional biophysical methods on recombinant PfP2\",\n      \"pmids\": [\"29124138\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of molten-globule character in vivo untested\", \"No atomic structure of the tetramer\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Reconstituting the P-stalk answered how PfP2 integrates into the ribosome, revealing a one-step trilateral assembly and framing the homo-oligomer as an off-pathway, functionally distinct species.\",\n      \"evidence\": \"Tricistronic bacterial expression of the P. falciparum P-stalk, bacterial two-hybrid, mass spectrometry, and biophysical analyses\",\n      \"pmids\": [\"25450178\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometric partitioning between ribosomal and off-pathway pools in the parasite unknown\", \"Trigger diverting PfP2 to the non-ribosomal pathway not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Detecting PfP2 on the merozoite surface and blocking invasion with anti-PfP2 antibodies extended its extra-ribosomal role to a second cell-cycle stage.\",\n      \"evidence\": \"P2-specific antibody surface detection and invasion-inhibition assay in P. falciparum\",\n      \"pmids\": [\"25280460\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Merozoite-surface binding partner not identified\", \"Mechanism by which surface PfP2 contributes to invasion unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Characterizing the C-terminal domain established that it is intrinsically disordered independent of oligomeric state, separating the folded self-associating core from the flexible tail.\",\n      \"evidence\": \"Gel filtration, CD, and NMR HSQC of the isolated C-terminal domain, plus 15N relaxation across urea concentrations\",\n      \"pmids\": [\"25412900\", \"25747872\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional role of the disordered C-terminus in ribosomal or surface activity not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identifying Band 3 as the erythrocyte receptor answered how surface PfP2 anchors to the host membrane and localized the interaction to the hydrophobic N-terminal domain.\",\n      \"evidence\": \"NMR binding studies, erythrocyte pull-down, immunoprecipitation, mass spectrometry, and neuraminidase/trypsin treatment; TgP2 negative control\",\n      \"pmids\": [\"32717409\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Binding stoichiometry and affinity to Band 3 not quantified\", \"Whether Band 3 binding is required for fatty-acid import not directly tested here\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linking the surface tetramer to serum fatty-acid import and defining a Met-oxidation stabilization plus Cys12/Cys53 redox switch answered how PfP2 physically supports schizogony.\",\n      \"evidence\": \"Fatty-acid import assays with reversible blockage in synchronized P. falciparum and biochemical characterization of Met-O-Met and Cys-Cys redox states\",\n      \"pmids\": [\"38726364\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transport mechanism moving fatty acids from surface PfP2 into the parasite unresolved\", \"Enzymes controlling the Met oxidation and disulfide redox states not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the parasite partitions PfP2 between its ribosomal P-stalk role and its exported surface fatty-acid-import role, and what machinery exports and modifies it, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Export pathway to the IE surface unknown\", \"Regulatory trigger for off-pathway homo-tetramer formation undefined\", \"Enzymes controlling Met-O-Met and Cys redox modifications unidentified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003735\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0005543\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0022625\", \"supporting_discovery_ids\": [6, 1]},\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [0, 5, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0015908\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"GO:0051301\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"60S ribosomal P-stalk pentamer uL10/P0\\u2013(P1\\u2013PfP2)\\u2082 [#6]\",\n      \"PfP2 homo-tetramer (off-pathway, surface-exported) [#0, #4]\"\n    ],\n    \"partners\": [\n      \"P0 (uL10) ribosomal stalk protein [#6]\",\n      \"P1 ribosomal stalk protein [#6]\",\n      \"erythrocytic Band 3 [#9]\"\n    ],\n    \"other_free_text\": [\n      \"SDS/denaturation-resistant homo-tetramer exported to the infected-erythrocyte surface at 26\\u201328 h post-invasion; anti-PfP2 antibody blockade reversibly arrests first nuclear division and fragments the tubovesicular network [#0]\",\n      \"Self-association nucleates at the N-terminal Met1\\u2013Leu14 hydrophobic segment; C-terminal ~45\\u201350 residues are intrinsically disordered regardless of oligomeric state [#3, #7, #8]\",\n      \"Tetramer retains molten-globule character at physiological pH [#4]\",\n      \"Denaturation resistance mediated by Met11\\u2013O\\u2013Met11 linkages; Cys12/Cys53 disulfide redox switch controls fatty-acid binding and release [#10]\",\n      \"Erythrocyte binding is neuraminidase-resistant but trypsin-sensitive; the homologous TgP2 does not bind erythrocytes [#9]\",\n      \"Localizes to the merozoite surface; anti-PfP2 antibodies inhibit invasion [#5]\",\n      \"Stage-specific parasite extracts (24\\u201336 h post-invasion) induce DTT/SDS-resistant oligomerization of recombinant PfP2, requiring multiple parasite proteins [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0309600","name":null,"product":"60S acidic ribosomal protein P2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0407700","name":null,"product":"60S acidic ribosomal protein P2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0833100","name":null,"product":"60S acidic ribosomal protein P2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PfP2","evaluation":null}