Affinage · Plasmodium

EBA175

PF3D7_0731500 · erythrocyte binding antigen-175

Annotated
2026-09-08
95 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EBA-175 (PF3D7_0731500) is a Plasmodium falciparum merozoite microneme adhesin that mediates sialic acid-dependent erythrocyte recognition during blood-stage invasion (PMID:3901257, PMID:10861015). Its erythrocyte-binding activity resides in the cysteine-rich region II (RII), which specifically engages the terminal Neu5Ac(α2-3)Gal sequences of O-linked glycans on glycophorin A, requiring both sialic acid and the glycophorin A peptide backbone (PMID:1310320, PMID:8009226); RII adopts a two-domain (F1/F2) Duffy binding-like fold that dimerizes to create glycan-binding channels, with F2 making the majority of glycan contacts (PMID:16051144), and full ectodomain contributions outside RII further support glycophorin A engagement (PMID:24043627). Receptor engagement is not merely adhesive: EBA-175 binding to glycophorin A, with CD44 acting as a coreceptor, drives erythrocyte cytoskeletal phosphorylation, increases cytoskeletal tension and lowers the membrane bending modulus, biophysically priming the red cell for invasion (PMID:28373555, PMID:28226242, PMID:37832027), and functions upstream of downstream invasion signals including calcium restoration and rhoptry protein release (PMID:20140184, PMID:23387921). Genetic disruption inactivates the EBA-175/glycophorin A route and, in strains such as W2mef, triggers a stable switch to sialic acid-independent invasion, defining EBA-175 as one interchangeable ligand within a redundant invasion-pathway network alongside the PfRh proteins (PMID:10861015, PMID:12672957, PMID:21149582). EBA-175 is secreted upon a low-potassium/phospholipase C/calcium signal, and is shed from the merozoite surface by the rhomboid protease PfROM4, which cleaves within its transmembrane domain around the time of invasion (PMID:17000879, PMID:20140184).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1985 Medium

    Establishing that a secreted parasite antigen could bridge merozoites and susceptible erythrocytes framed EBA-175 as a candidate invasion ligand rather than a passive surface protein.

    Evidence erythrocyte binding assays with culture supernatants and cross-strain invasion inhibition in vitro

    PMID:3901257

    Open questions at the time
    • Molecular receptor not identified
    • Binding domain within the protein not mapped
  2. 1990 High

    Cloning the single-ORF gene and demonstrating that a surface-exposed peptide region elicits invasion-blocking antibodies connected the protein sequence to functional invasion and binding.

    Evidence gene sequencing plus rabbit immunization with a synthetic peptide followed by invasion and binding inhibition assays

    PMID:2229177

    Open questions at the time
    • Receptor identity unresolved
    • Precise binding domain not yet delimited
  3. 1990 Medium

    Showing that a 190-kDa precursor is processed to 175 kDa and released at schizont rupture in a protease-dependent manner established that EBA-175 is proteolytically shed.

    Evidence biochemical fractionation, Western blot, and protease inhibitor treatment of schizont-infected erythrocytes

    PMID:2194125

    Open questions at the time
    • Responsible protease not identified
    • Cleavage site not mapped
  4. 1992 High

    Defining Neu5Ac(α2-3)Gal on glycophorin A as the binding determinant identified the molecular receptor and its precise glycan linkage requirement.

    Evidence competitive oligosaccharide inhibition, co-immunoprecipitation with anti-glycophorin A, enzyme-modified erythrocyte binding, and influenza C esterase discrimination of Neu5Ac vs Neu5,9Ac2

    PMID:1310320 PMID:1565137

    Open questions at the time
    • Contribution of the peptide backbone not yet quantified
    • Binding domain within EBA-175 not localized
  5. 1994 High

    Mapping binding to the cysteine-rich region II and to glycophorin A (not B) localized the functional ligand domain and defined receptor specificity.

    Evidence expression of truncated constructs on COS cells and binding assays with glycophorin-variant and glycophorin-deficient erythrocytes

    PMID:8009226 PMID:8078523

    Open questions at the time
    • Atomic basis of glycan recognition unknown
    • Role of the glycophorin B ligand not attributable to EBA-175
  6. 2000 High

    Genetic disruption showed EBA-175 is functionally dispensable in some backgrounds because parasites switch to sialic acid-independent invasion, revealing invasion-pathway redundancy.

    Evidence targeted gene disruption in W2mef and Dd2/Nm with expression, localization, and sialic-acid-dependence invasion readouts

    PMID:10861015 PMID:10989151

    Open questions at the time
    • Molecular basis of the pathway switch not defined
    • Compensating ligands not identified
  7. 2002 Medium

    Stage-specific transcription peaking late in schizogony and independent trafficking of EBA-175 relative to AMA1 clarified the timing and organellar logistics of the ligand's deployment.

    Evidence quantitative RT-PCR in synchronized parasites and parallel immunofluorescence/Western tracking of EBA-175 and AMA1 processing

    PMID:12000842 PMID:12228305

    Open questions at the time
    • Transcriptional regulators not identified
    • Trafficking signal not yet mapped
  8. 2003 High

    Domain-swap and knockout experiments dissected functional domains: the cytoplasmic tail carries invasion-essential (but not trafficking) information and is interchangeable with TRAP, while the EBA-175/glycophorin A axis is the major chymotrypsin-resistant pathway.

    Evidence domain-swap transgenics with functional rescue and localization, plus knockout/truncation lines assayed against enzyme-treated erythrocytes across strains

    PMID:12672957 PMID:12876279

    Open questions at the time
    • Cytoplasmic-domain effector machinery not identified
    • Strain-dependence of pathway switching unexplained
  9. 2005 High

    The atomic structure of RII revealed a two-DBL-domain (F1/F2) monomer that dimerizes to form glycan-binding channels, providing the structural mechanism of sialylated-glycan recognition and its evolved preference for human Neu5Ac.

    Evidence X-ray crystallography of RII-glycan complex and comparative sialic-acid binding assays with P. falciparum and P. reichenowi orthologs

    PMID:16051144 PMID:16126901

    Open questions at the time
    • Structure of full ectodomain-glycophorin A complex unresolved
    • Coupling of binding to signaling not structurally defined
  10. 2006 High

    Identifying PfROM4 as the intramembrane protease that cleaves the EBA-175 transmembrane domain, along with the cysteine-rich ectodomain microneme-targeting signal, resolved how EBA-175 is trafficked and shed and showed cleavage is essential for growth.

    Evidence heterologous rhomboid cleavage assays, transmembrane mutagenesis and domain swaps, EBA-GFP chimera localization, and in vitro folding with PfPDI-8

    PMID:16806221 PMID:16935855 PMID:17000879 PMID:17040128

    Open questions at the time
    • In vivo timing and regulation of shedding not fully resolved
    • Functional requirement of PfPDI-8 folding in vivo not established
  11. 2010 High

    Linking low-potassium/phospholipase-C/calcium signaling to EBA-175 secretion, and cooperative function with PfRh proteins, placed EBA-175 within an ordered, network-regulated invasion cascade.

    Evidence live calcium imaging, flow cytometry, PLC inhibition, and single/double ebl-PfRh knockouts with invasion and transcriptional profiling

    PMID:20140184 PMID:21149582

    Open questions at the time
    • Molecular sensor coupling secretion to calcium not identified
    • Mechanism of cross-family transcriptional compensation unknown
  12. 2013 High

    Antibody-complex structures, full-ectodomain binding quantification, and epistasis with PfTRAMP defined how inhibitory antibodies block glycophorin A engagement and positioned EBA-175 upstream of rhoptry release.

    Evidence crystallography and SAXS of RII-antibody complexes, SPR-type binding of full-length ectodomain, and invasion inhibition with antibody combinations

    PMID:23387921 PMID:23717209 PMID:24043627

    Open questions at the time
    • Signal relayed from receptor binding to rhoptry secretion not molecularly traced
    • Role of non-DBL regions in vivo not defined
  13. 2017 Medium

    Demonstrating that EBA-175-glycophorin A engagement drives erythrocyte cytoskeletal phosphorylation and measurable biophysical changes reframed EBA-175 as an active signaling ligand that primes the host cell for invasion.

    Evidence deformability cytometry, flicker spectroscopy, phosphoproteomics, and TRPM7 kinase inhibition with invasion readouts

    PMID:28226242 PMID:28373555

    Open questions at the time
    • Host receptor coupling the ligand to TRPM7 signaling not defined at this stage
    • Causal chain from tension change to invasion not fully resolved
  14. 2018 Medium

    Epigenetic silencing of eba-175 showed that transcriptional control of the ligand itself governs invasion-pathway usage, connecting gene regulation to phenotypic pathway switching.

    Evidence CRISPR/dCas9 epigenetic editing at the eba-175 TSS with expression and invasion-pathway assays

    PMID:30584102

    Open questions at the time
    • Endogenous epigenetic regulators not identified
    • Trigger for physiological switching unknown
  15. 2024 High

    Identifying CD44 as a coreceptor and showing EBA-175 acts as a CD44 cross-linker that increases Basigin accessibility for the PfRH5/PCRCR complex mechanistically linked EBA-175 binding to downstream invasion-complex engagement and to attachment force.

    Evidence CD44 knockout erythroid cells, recombinant EBA-175 treatment with Basigin/PfRH5 binding and surface-accessibility readouts, and optical-tweezer force measurements of attachment

    PMID:37832027 PMID:39312588 PMID:41354647

    Open questions at the time
    • Structural basis of EBA-175-CD44 interaction unknown
    • How glycophorin A and CD44 engagement are integrated not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How receptor engagement is mechanistically transduced into the erythrocyte signaling and membrane-remodeling events, and how the cytoplasmic-tail invasion machinery operates, remain unresolved.
  • Molecular link from glycophorin A/CD44 binding to the erythrocyte phosphorylation cascade not fully defined
  • Effectors engaged by the EBA-175 cytoplasmic domain unidentified
  • Integration of glycophorin A, CD44, and Basigin engagement into a single invasion mechanism unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
CD44 (ERYTHROCYTE CORECEPTOR / CROSS-LINKING TARGET) [#27, #28]GLYCOPHORIN A (HUMAN ERYTHROCYTE RECEPTOR, NEU5AC(Α2-3)GAL GLYCANS) [#3, #5, #6, #22]PFPDI-8 (PROTEIN DISULFIDE ISOMERASE ASSISTING EBA-175 FOLDING IN VITRO) [#18]PFRH FAMILY PROTEINS (COOPERATIVE/COMPENSATORY INVASION FUNCTION) [#20]PFRH5/PCRCR COMPLEX AND BASIGIN (ACCESSIBILITY ENHANCED BY EBA-175-CD44 ACTION) [#28]PFROM4 (RHOMBOID INTRAMEMBRANE PROTEASE THAT CLEAVES THE EBA-175 TM DOMAIN) [#15, #17]PFTRAMP (RHOPTRY PROTEIN RELEASED DOWNSTREAM OF EBA-175 ENGAGEMENT) [#23]
Complex memberships
EBA-175 region II forms a homodimer that creates glycan-binding channels [#13]Full-length EBA-175 ectodomain can self-associate [#22]

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 EBA-175 (175-kDa antigen) binds to human erythrocytes susceptible to invasion in a strain-specific manner, and also binds to merozoites. Erythrocytes coated with EBA-175 from one strain were partially resistant to invasion by heterologous-strain merozoites, suggesting EBA-175 acts as a bridging receptor between erythrocytes and merozoites. Erythrocyte binding assay with culture supernatants; cross-strain binding inhibition of merozoite invasion in vitro Science Medium 3901257
1990 EBA-175 is encoded by a single open reading frame of 1,435 amino acids. A synthetic peptide (EBA-peptide 4, residues 1062-1103) elicited antibodies in rabbits that inhibited merozoite invasion of erythrocytes in vitro by ~80% and blocked EBA-175 binding to erythrocytes, demonstrating this region is surface-exposed and functionally important. DNA sequencing of the EBA-175 gene; immunization with synthetic peptide; invasion inhibition assay; erythrocyte binding inhibition assay The Journal of cell biology High 2229177
1990 EBA-175 is expressed during schizogony as a 190-kDa precursor in the cell pellet, processed to a 175-kDa form that is released into culture supernatant upon schizont rupture. Release is inhibited by the protease inhibitors chymostatin and leupeptin, indicating proteolytic processing is required for shedding. Western blot, isoelectric focusing, fractionation of schizont-infected erythrocytes, protease inhibitor treatment Molecular and biochemical parasitology Medium 2194125
1992 EBA-175 binds specifically to the terminal Neu5Ac(α2-3)Gal sequences on O-linked tetrasaccharides of glycophorin A. Binding was competitively inhibited by Neu5Ac(α2-3)Gal-containing oligosaccharides but not by Neu5Ac(α2-6)Gal linkages. EBA-175 bound tightly enough to glycophorin A to be co-precipitated with an anti-glycophorin A antibody. Competitive binding inhibition with soluble oligosaccharides; co-immunoprecipitation with anti-glycophorin A antibody; binding assays with enzyme-modified erythrocytes The Journal of cell biology High 1310320
1992 EBA-175 binding to mouse erythrocytes (which naturally contain Neu5,9Ac2) is increased when the C-9 acetyl group is removed by influenza C virus esterase (converting Neu5,9Ac2 to Neu5Ac), demonstrating that EBA-175 discriminates between Neu5Ac and Neu5,9Ac2 and that sialic acid is a structural component of the invasion receptor. EBA-175 binding assay to mouse erythrocytes treated with sialidase or influenza C virus esterase; invasion assay Molecular and biochemical parasitology Medium 1565137
1994 Region II of EBA-175, a cysteine-rich domain, is the erythrocyte-binding domain. When expressed on COS cells, Region II bound specifically to glycophorin A but not glycophorin B, and binding required both sialic acid and the peptide backbone of glycophorin A. Expression of truncated EBA-175 constructs on COS cells; erythrocyte binding assay with glycophorin-variant erythrocytes Science High 8009226
1994 EBA-175 binds predominantly to glycophorin A (not glycophorin B) based on binding assays using glycophorin A-deficient erythrocytes. The glycophorin B invasion pathway uses a different parasite ligand, distinct from EBA-175. Erythrocyte binding assay with glycophorin-deficient erythrocytes; enzyme-treated erythrocyte invasion assays Molecular and biochemical parasitology Medium 8078523
2000 Targeted disruption of the 3'-cysteine rich region, transmembrane, and cytoplasmic domains of EBA-175 (in W2mef) did not affect protein expression level or subcellular localization, nor the release of soluble EBA-175 after schizont rupture. However, disruption functionally inactivated the EBA-175/glycophorin A invasion route, causing mutant parasites to switch stably to sialic acid-independent invasion (~85% of invasion). Targeted gene disruption; Western blot for protein expression; subcellular localization analysis; sialic acid-dependent invasion assay Proceedings of the National Academy of Sciences High 10861015
2000 Disruption of the C-terminal region of EBA-175 in the Dd2/Nm clone (which uses a sialic acid-independent invasion pathway) did not affect erythrocyte invasion rates. The truncated protein remained localized to the apical end near micronemes, indicating that the C-terminal region 6 and cytoplasmic domain are not required for microneme trafficking in this strain background. Targeted gene disruption; immunofluorescence localization; invasion assay with enzyme-treated erythrocytes Molecular and biochemical parasitology Medium 10989151
2002 EBA-175 and PfAMA1 are both localized to microneme organelles but translocate to the merozoite surface independently of each other, as demonstrated by tracking processed versus unprocessed forms in developing schizonts. Immunofluorescence; Western blot tracking processing and surface expression of EBA-175 and AMA1 in parallel Infection and immunity Medium 12228305
2002 EBA-175 transcript (eba-175) is expressed in a tightly controlled, stage-specific manner, peaking only at the end of schizont development, as demonstrated by quantitative real-time RT-PCR in synchronized parasites. Quantitative real-time RT-PCR (TaqMan) on temperature-synchronized P. falciparum Nucleic acids research Medium 12000842
2003 Genetic knockout or truncation of EBA-175 in W2mef parasites (which are sialic acid-dependent) caused a switch to sialic acid-independent invasion, while 3D7 parasites lacking EBA-175 showed no change in sialic acid-independent invasion ability. Both W2mef and 3D7 EBA-175 knockout lines invaded chymotrypsin-treated erythrocytes inefficiently, identifying the EBA-175/glycophorin A interaction as the major chymotrypsin-resistant invasion pathway. Gene knockout and truncation in two P. falciparum strains; invasion assays with neuraminidase-, chymotrypsin-, and trypsin-treated erythrocytes Proceedings of the National Academy of Sciences High 12672957
2003 The cytoplasmic domain of EBA-175 encodes information essential for merozoite invasion function but is dispensable for trafficking of the protein to micronemes. Furthermore, the cytoplasmic domain of TRAP can substitute for that of EBA-175, restoring invasion function, indicating a shared cytoplasmic machinery for invasion regardless of parasite stage or host cell type. Domain-swap transgenic parasites; immunofluorescence localization; invasion assay The Journal of cell biology High 12876279
2005 Crystal structure of EBA-175 region II (RII) was solved at atomic resolution. RII forms a dimer with two prominent channels containing four of six glycan-binding sites. Each monomer consists of two Duffy binding-like (DBL) domains (F1 and F2), with F2 making the majority of glycan contacts. Sialylated glycan (Neu5Ac-containing) binding sites were identified in a complex of RII with a glycan containing essential components for receptor binding. X-ray crystallography; RII-glycan co-crystal structure Cell High 16051144
2005 P. falciparum EBA-175 evolved to preferentially recognize N-acetylneuraminic acid (Neu5Ac), the predominant sialic acid on human erythrocytes (humans having lost the ability to synthesize N-glycolylneuraminic acid, Neu5Gc). This was demonstrated using erythroleukemia cells with experimentally manipulated sialic acid content, showing that P. falciparum EBA-175 binds human-type Neu5Ac-bearing cells efficiently, whereas P. reichenowi EBA-175 prefers Neu5Gc-bearing cells. Modified sialic acid binding assay; erythroleukemia cells with manipulated Sia content; binding of EBA-175 orthologs from P. falciparum and P. reichenowi Proceedings of the National Academy of Sciences Medium 16126901
2006 EBA-175 is cleaved within its transmembrane domain by PfROM4, a rhomboid intramembrane protease localized to the merozoite plasma membrane, at a site conserved across the DBL-EBP family. Shedding of EBA-175 from the merozoite surface occurs around the time of erythrocyte invasion. Mutations within the EBA-175 transmembrane domain that abolish PfROM4 cleavage prevented parasite growth. Heterologous cleavage assay with Plasmodium and model rhomboid proteases; mutagenesis of the EBA-175 transmembrane domain; transgenic parasite growth assay; immunofluorescence timing of shedding The Journal of cell biology High 17000879
2006 EBA-175 (along with EBA-140 and EBA-181) is trafficked to micronemes via a conserved cysteine-rich region in the ectodomain, not through its cytoplasmic or transmembrane domains. Correct sorting to micronemes is dependent on accurate timing of expression, as shown by analysis of EBA-GFP chimeric protein distribution in transgenic parasites. Transgenic EBA-GFP chimeric proteins; immunofluorescence localization; domain-swap analysis in P. falciparum The Journal of biological chemistry Medium 16935855
2006 PfROM4 cleaved EBA-175 (along with TRAP, CTRP, MTRAP, PFF0800c, BAEBL, JESEBL, MAEBL, Rh1, Rh2a, Rh2b, Rh4) efficiently in a heterologous assay; cleavage was dependent on the adhesin transmembrane domains. Swapping transmembrane regions between BAEBL and AMA1 switched the cleavage preferences of PfROMs 1 and 4, confirming that the transmembrane domain determines substrate specificity. Heterologous rhomboid protease cleavage assay; transmembrane domain swap experiments PLoS pathogens Medium 17040128
2006 Protein disulfide isomerase PfPDI-8 facilitates disulfide-dependent conformational folding of EBA-175 in vitro, demonstrated by biochemical reconstitution showing PfPDI-8 is a potent oxido-reductase that assists in the proper folding of recombinant EBA-175. Biochemical oxido-reductase assay; in vitro protein folding reconstitution with recombinant PfPDI-8 and EBA-175 International journal for parasitology Medium 16806221
2010 Exposure of P. falciparum merozoites to low potassium ion concentrations (as in blood plasma) triggers a rise in cytosolic calcium via a phospholipase C-mediated pathway, which then drives secretion of EBA-175 from micronemes to the merozoite surface. Subsequently, EBA-175 interaction with its receptor glycophorin A restores basal cytosolic calcium levels and triggers rhoptry protein release. Time-lapse video microscopy of intracellular calcium in merozoites; flow cytometry for cytosolic calcium and surface expression of apical organelle proteins; pharmacological inhibition of phospholipase C PLoS pathogens High 20140184
2010 EBA-175, EBA-181, and EBA-140 (EBL proteins) function cooperatively with PfRh (reticulocyte binding-like) proteins in erythrocyte invasion. Loss of EBA-181 function ablates antibody inhibition mediated by PfRh2a/b, and loss of some ebl genes results in upregulation of PfRh family transcripts, demonstrating functional interaction and compensatory regulation between the two families. Single and double gene knockouts (eba-175, eba-181, eba-140); invasion assays; antibody growth inhibition assays; transcriptional profiling Infection and immunity High 21149582
2013 Structural basis for antibody inhibition of EBA-175 was established by X-ray crystallography and small-angle X-ray scattering. The potent inhibitory antibody R217 engages critical glycophorin A (GpA)-binding residues and the proposed dimer interface of EBA-175 RII, directly blocking GpA engagement. A weakly inhibitory antibody R218 binds an asparagine-rich surface loop and does not prevent GpA binding. X-ray crystallography of antibody-RII complexes; small-angle X-ray scattering; direct receptor binding assay; epitope mapping PLoS pathogens High 23717209
2013 The full ectodomain of EBA-175 (PfEBA175 FL) binds native glycophorin A with a KD of ~0.26 μM and can self-associate. The region II (RII) fragment alone bound glycophorin A with lower affinity, demonstrating that regions outside the DBL domains are important for GYPA interaction. Antibodies directed to non-DBL regions also contribute to invasion inhibition. Recombinant expression of full-length EBA-175 ectodomain; quantitative binding assay (SPR or equivalent); invasion inhibition with anti-non-DBL antibodies The Journal of biological chemistry Medium 24043627
2013 EBA-175 interaction with glycophorin A triggers secretion of rhoptry protein PfTRAMP from rhoptries during erythrocyte invasion. Antibodies against PfTRAMP block invasion, and combination of anti-PfTRAMP and anti-EBA-175 antibodies shows additive invasion inhibition, placing EBA-175 upstream of rhoptry protein release in the invasion cascade. Localization studies (immunofluorescence); invasion inhibition assays with antibody combinations; functional dissection of secretion sequence Cellular microbiology Medium 23387921
2017 EBA-175 binding to glycophorin A on the erythrocyte surface triggers an increase in cytoskeletal tension and a reduction in the bending modulus of the red cell membrane. The reduction in bending modulus is directly correlated with parasite invasion efficiency, indicating EBA-175 primes the erythrocyte biophysically to facilitate invasion. Real-time deformability cytometry; flicker spectroscopy; quantitative correlation of membrane biophysical changes with invasion efficiency Proceedings of the National Academy of Sciences Medium 28373555
2017 EBA-175 binding to glycophorin A activates a phosphorylation cascade in erythrocyte cytoskeletal proteins that alters the viscoelastic properties of the host cell membrane, conditioning it for successful invasion. TRPM7 kinase inhibitors (FTY720 and waixenicin A) block this phosphorylation cascade, inhibiting the deformability change and merozoite invasion. Erythrocyte deformability assay; phosphoproteomics of EBA-175-treated erythrocytes; pharmacological inhibition of TRPM7 kinase; invasion inhibition assay eLife Medium 28226242
2018 Epigenetic repression of eba-175 using a CRISPR/dCas9 system fused to an epigenetic effector domain (erasing histone acetylation at the eba-175 transcription start site) significantly reduced EBA-175 expression and caused a switch in the parasite's invasion pathway, demonstrating that transcriptional regulation of eba-175 controls invasion pathway usage. CRISPR/dCas9 epigenetic editing (histone deacetylation at eba-175 TSS); RT-PCR/Western blot for expression; invasion pathway assay Proceedings of the National Academy of Sciences Medium 30584102
2023 EBA-175 interacts with the erythrocyte transmembrane protein CD44 and induces phosphorylation of erythrocyte cytoskeletal proteins in a CD44-dependent manner. P. falciparum invasion is reduced in CD44-null cultured red blood cells. The primary erythrocyte binding of EBA-175 relies on its canonical receptor glycophorin A, with CD44 acting as a coreceptor. CRISPR/Cas9 knockout of CD44 in primary human hematopoietic stem cells; ex vivo erythropoiesis; invasion assay; binding assay with receptor-deficient cells; phosphorylation assay Blood High 37832027
2024 EBA-175 interacts with CD44 on erythrocytes and induces RBC membrane changes that increase accessibility of surface proteins including Basigin, and enhance binding of the PfRH5/PCRCR invasion complex to Basigin. These effects are similar to those of an anti-CD44 cross-linking antibody (BRIC 222), suggesting EBA-175 acts as a functional CD44 cross-linker to coordinate downstream invasion interactions. Recombinant EBA-175 treatment of RBCs; binding assay for PfRH5/PCRCR to Basigin; flow cytometry for surface protein accessibility; P. falciparum invasion assay with EBA-175 addition Nature communications Medium 41354647
2024 Optical tweezer-based quantification showed that interventions disrupting EBA-175-like antigen (PfEBA) family function significantly reduced the force and frequency of merozoite-erythrocyte attachment. Deletion of EBA-175 (PfEBA175) had a significant impact on invasion under flow conditions but not in static culture, establishing PfEBA family proteins (including EBA-175) as central mediators of merozoite attachment. Optical tweezers direct force measurement of merozoite-erythrocyte attachment; genetically modified parasite lines; invasion assay under flow and static conditions PLoS pathogens Medium 39312588
2009 EBA-175 region II polymorphisms (high sequence variability between strains) do not affect the receptor specificity or the ability of EBA-175 to bind glycophorin A; unlike EBA-140 and EBA-181, EBA-175 shows no variability in its ability to bind its receptor despite high polymorphism in region II. Erythrocyte binding assays with recombinant region II variants; invasion assays with receptor-deficient erythrocytes Infection and immunity Medium 19204093

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Receptor and ligand domains for invasion of erythrocytes by Plasmodium falciparum. Science (New York, N.Y.) 477 8009226
2008 Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria. Infection and immunity 324 18316390
1985 A Plasmodium falciparum antigen that binds to host erythrocytes and merozoites. Science (New York, N.Y.) 309 3901257
2005 Structural basis for the EBA-175 erythrocyte invasion pathway of the malaria parasite Plasmodium falciparum. Cell 273 16051144
2010 The relationship between anti-merozoite antibodies and incidence of Plasmodium falciparum malaria: A systematic review and meta-analysis. PLoS medicine 271 20098724
2010 Distinct external signals trigger sequential release of apical organelles during erythrocyte invasion by malaria parasites. PLoS pathogens 225 20140184
1998 Genetic polymorphism and natural selection in the malaria parasite Plasmodium falciparum. Genetics 213 9584096
1992 A malaria invasion receptor, the 175-kilodalton erythrocyte binding antigen of Plasmodium falciparum recognizes the terminal Neu5Ac(alpha 2-3)Gal- sequences of glycophorin A. The Journal of cell biology 206 1310320
1990 Primary structure of the 175K Plasmodium falciparum erythrocyte binding antigen and identification of a peptide which elicits antibodies that inhibit malaria merozoite invasion. The Journal of cell biology 206 2229177
2005 Structural basis for Duffy recognition by the malaria parasite Duffy-binding-like domain. Nature 204 16372020
2003 Erythrocyte-binding antigen 175 mediates invasion in Plasmodium falciparum utilizing sialic acid-dependent and -independent pathways. Proceedings of the National Academy of Sciences of the United States of America 192 12672957
2014 Efficient CRISPR-Cas9-mediated genome editing in Plasmodium falciparum. Nature methods 182 25108687
2006 Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria. PLoS pathogens 180 17040128
2000 Targeted disruption of an erythrocyte binding antigen in Plasmodium falciparum is associated with a switch toward a sialic acid-independent pathway of invasion. Proceedings of the National Academy of Sciences of the United States of America 172 10861015
2001 A Plasmodium falciparum homologue of Plasmodium vivax reticulocyte binding protein (PvRBP1) defines a trypsin-resistant erythrocyte invasion pathway. The Journal of experimental medicine 169 11733572
1994 Glycophorin B as an EBA-175 independent Plasmodium falciparum receptor of human erythrocytes. Molecular and biochemical parasitology 169 8078523
2010 Association between naturally acquired antibodies to erythrocyte-binding antigens of Plasmodium falciparum and protection from malaria and high-density parasitemia. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 168 20843207
2003 A novel erythrocyte binding antigen-175 paralogue from Plasmodium falciparum defines a new trypsin-resistant receptor on human erythrocytes. The Journal of biological chemistry 153 12556470
2007 IgG antibody responses to Plasmodium falciparum merozoite antigens in Kenyan children have a short half-life. Malaria journal 152 17598897
2002 Independent translocation of two micronemal proteins in developing Plasmodium falciparum merozoites. Infection and immunity 152 12228305
2006 Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite. The Journal of cell biology 151 17000879
2008 Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies. The Journal of clinical investigation 150 18064303
2005 Evolution of human-chimpanzee differences in malaria susceptibility: relationship to human genetic loss of N-glycolylneuraminic acid. Proceedings of the National Academy of Sciences of the United States of America 148 16126901
2001 Characterization of a Plasmodium falciparum erythrocyte-binding protein paralogous to EBA-175. Proceedings of the National Academy of Sciences of the United States of America 140 11309486
1999 Plasmodium falciparum field isolates commonly use erythrocyte invasion pathways that are independent of sialic acid residues of glycophorin A. Infection and immunity 138 10531229
1991 Determination of genetic variation within Plasmodium falciparum by using enzymatically amplified DNA from filter paper disks impregnated with whole blood. Journal of clinical microbiology 131 1864936
2010 Reticulocyte and erythrocyte binding-like proteins function cooperatively in invasion of human erythrocytes by malaria parasites. Infection and immunity 117 21149582
2005 Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection. The American journal of tropical medicine and hygiene 104 16014863
2002 Bacterially expressed and refolded receptor binding domain of Plasmodium falciparum EBA-175 elicits invasion inhibitory antibodies. Molecular and biochemical parasitology 99 12165386
2013 RH5-Basigin interaction plays a major role in the host tropism of Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America 98 24297912
2009 Contrasting population structures of the genes encoding ten leading vaccine-candidate antigens of the human malaria parasite, Plasmodium falciparum. PloS one 91 20041125
2001 Codon optimization of gene fragments encoding Plasmodium falciparum merzoite proteins enhances DNA vaccine protein expression and immunogenicity in mice. Infection and immunity 91 11705894
2004 Polymorphism in the Plasmodium falciparum erythrocyte-binding ligand JESEBL/EBA-181 alters its receptor specificity. Proceedings of the National Academy of Sciences of the United States of America 85 14983041
2003 Effect of codon optimization on expression levels of a functionally folded malaria vaccine candidate in prokaryotic and eukaryotic expression systems. Infection and immunity 85 12933838
2000 Plasmodium falciparum EBA-175 kDa protein peptides which bind to human red blood cells. Parasitology 81 10759080
2003 Erythrocyte invasion phenotypes of Plasmodium falciparum in The Gambia. Infection and immunity 80 12654801
1990 Characterization of the 175-kilodalton erythrocyte binding antigen of Plasmodium falciparum. Molecular and biochemical parasitology 79 2194125
2000 Antibodies against the Plasmodium falciparum receptor binding domain of EBA-175 block invasion pathways that do not involve sialic acids. Infection and immunity 78 10722589
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2005 Distinct Th1- and Th2-Type prenatal cytokine responses to Plasmodium falciparum erythrocyte invasion ligands. Infection and immunity 75 15908375
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