Affinage · Plasmodium

RON2

PF3D7_1452000 · rhoptry neck protein 2

Annotated
2026-09-08
63 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RON2 (PF3D7_1452000) is a rhoptry neck protein that serves as the parasite-supplied membrane anchor of the moving junction, the tight-junction structure through which apicomplexan parasites invade host cells (PMID:18952195, PMID:21347343). In P. falciparum merozoites, RON2 localizes to the neck of the rhoptry, peaks in transcription at the mature schizont stage, and is discharged early during invasion, after which it is inserted as an integral membrane protein into the host erythrocyte membrane (PMID:18952195, PMID:21347343, PMID:23049965). Its extracellular region binds the hydrophobic groove of the parasite surface protein AMA1 in a manner that requires two conserved, disulfide-linked cysteines in the RON2 peptide, and this AMA1-RON2 engagement triggers tight-junction formation that anchors the parasite and commits the merozoite to invasion (PMID:21347343, PMID:21788485, PMID:22737069). Junction formation via AMA1-RON2 is a molecularly distinct step from parasitophorous vacuole formation and occurs downstream of the PfRh5-basigin binding step in the invasion sequence (PMID:21788485, PMID:25723550). A cryo-EM structure of the endogenous complex shows a 1:1:1:1 assembly of AMA1 with RON2, RON4, and RON5, in which two RON2 transmembrane helices anchor the complex in the erythrocyte membrane and present an extracellular handle for AMA1 binding, while the RON2/4/5 platform inside the red cell electrostatically engages and embeds into the membrane bilayer, implicating RON2 in host membrane remodeling (PMID:42379167). Beyond its erythrocytic role, RON2 also localizes to rhoptries in sporozoites and is required for invasion of both mosquito salivary glands and mammalian hepatocytes, where loss of a functional AMA1-RON complex alters the entry junction morphology (PMID:30307699, PMID:35731833). Notably, mutations in the AMA1 Loop1E that ablate RON2-loop binding do not impair erythrocyte invasion, indicating additional AMA1 interactions contribute and that the isolated AMA1-RON2 loop contact is not strictly essential (PMID:36847896).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2008 Medium

    Establishing that P. falciparum possesses a moving-junction complex was needed to test whether the apicomplexan invasion machinery is conserved beyond T. gondii; localizing RON2 to the rhoptry neck and showing it complexes with RON4 and AMA1 defined RON2 as a core junction component and excluded it from the RhopH complex.

    Evidence Co-immunoprecipitation, immunofluorescence, and transcriptional analysis in P. falciparum merozoites

    PMID:18952195

    Open questions at the time
    • Interaction shown by Co-IP without stoichiometry or direct binding interface
    • Functional requirement of RON2 for invasion not yet demonstrated
  2. 2011 High

    Whether RON2 acts on the parasite or host side of the junction and whether its AMA1 contact is functionally required were unresolved; showing RON2 inserts as an integral host-membrane protein and mapping its AMA1-binding extracellular region with invasion-blocking assays established RON2 as the host-membrane-anchored receptor for AMA1 driving entry.

    Evidence Membrane insertion assay, native/recombinant interaction assays, and invasion inhibition in P. falciparum

    PMID:21347343 PMID:22033736

    Open questions at the time
    • Molecular topology of the two transmembrane segments not yet defined
    • Nature of the host-membrane insertion mechanism unresolved
  3. 2011 High

    The chemistry of the RON2-AMA1 interface and its precise role in the invasion sequence were unknown; identifying two disulfide-linked cysteines as critical for binding to the AMA1 hydrophobic pocket and showing the RON2 peptide blocks junction but not vacuole formation established that this interaction triggers a discrete commitment step.

    Evidence AMA1 pocket mutants, RON2 peptide competition, antibody blocking, and live imaging of junction versus vacuole formation in P. falciparum

    PMID:21788485

    Open questions at the time
    • Structural basis of the disulfide-constrained peptide binding not yet resolved at atomic level
    • Relationship between RON2 peptide and full-length RON2 behavior not addressed
  4. 2012 High

    Atomic-resolution understanding of how RON2 engages AMA1 and whether the interface is a drug target were needed; crystallography of the AMA1-RON2 peptide complex defined the hydrophobic groove plus Domain-II-loop-displaced site and showed the RON2 peptide inhibits invasion irrespective of AMA1 polymorphism.

    Evidence X-ray crystallography, site-directed mutagenesis, binding and invasion inhibition assays in P. falciparum

    PMID:22737069

    Open questions at the time
    • Peptide-only structure does not capture the full-length transmembrane-anchored complex
    • Kinetics of complex formation and stabilization not addressed
  5. 2012 Medium

    The timing of RON2 secretion relative to junction formation was uncertain; high-definition imaging of endogenously tagged RON2 showed it is released early, among the first rhoptry neck proteins secreted during invasion.

    Evidence Endogenous gene tagging with live and fixed high-definition fluorescence imaging in P. falciparum

    PMID:23049965

    Open questions at the time
    • Mechanism of rhoptry discharge triggering not defined
    • Whether secretion timing differs across species not addressed
  6. 2015 High

    The position of the AMA1-RON2 junction within the ordered invasion cascade was unresolved; systematic blocking with live imaging placed AMA1-RON2-mediated tight-junction formation downstream of PfRh5-basigin binding, defining it as the anchoring step for internalization.

    Evidence Live cell imaging with genetic deletion, receptor cleavage, and inhibitory antibodies/peptides in P. falciparum

    PMID:23907321 PMID:25723550

    Open questions at the time
    • Molecular coupling between junction and the actomyosin motor not detailed
    • How the junction physically anchors internalization not structurally defined
  7. 2016 High

    Why the AMA1 Domain II loop matters for a productive junction was unclear; kinetic measurements showed the DII loop stabilizes the AMA1-RON2 complex 18-fold by slowing dissociation, revealing a post-binding locking mechanism.

    Evidence Fluorescence anisotropy kinetics, ITC, and a DII-loop deletion mutant in P. falciparum

    PMID:26731670

    Open questions at the time
    • Structural conformation of the locked state not directly visualized
    • Physiological consequence of altered half-life on invasion efficiency not quantified
  8. 2019 High

    Whether the disulfide-constrained RON2 conformation is a general binding requirement across Plasmodium species was untested; comparison of cyclic versus linear PvRON2 peptides showed the C2051-C2063 disulfide is essential for PvAMA1 binding, and cross-species structural work identified single residues driving species-specific recognition.

    Evidence SPR, ITC, CD, SAXS with cyclic/linear peptide comparison in P. vivax; crystallography and SPR across P. vivax and P. falciparum

    PMID:28817634 PMID:30683104

    Open questions at the time
    • Species-specificity determinants tested largely with peptides, not full-length proteins
    • Consequences for cross-species invasion in vivo not addressed
  9. 2023 High

    Whether the AMA1-RON2 loop contact is strictly essential for invasion was assumed but untested; mutating AMA1 Loop1E to ablate RON2 binding without impairing erythrocyte invasion showed the isolated loop interaction is dispensable and that additional AMA1 contacts contribute.

    Evidence Site-directed mutagenesis of AMA1 and RON2 with erythrocyte invasion and binding assays in P. falciparum and P. vivax

    PMID:36847896

    Open questions at the time
    • Identity of the compensating additional AMA1-RON2 contacts not defined
    • Whether redundancy applies to sporozoite invasion not tested
  10. 2018 High

    Whether RON2 functions beyond the blood stage was unknown; in P. berghei, sporozoite-stage-specific ron2 knockdown impaired salivary gland invasion by reducing attachment and reduced hepatocyte infectivity, establishing a distinct RON2 role in sporozoite invasion.

    Evidence Promoter-swap stage-specific knockdown with salivary gland and hepatocyte invasion assays in P. berghei

    PMID:30307699

    Open questions at the time
    • Whether sporozoite RON2 engages AMA1 in the same way as merozoite RON2 not established
    • Direct binding partners at the sporozoite junction not defined
  11. 2020 High

    How the sporozoite RON complex is assembled and trafficked was unknown; Co-IP from sporozoite extracts plus stage-specific knockdown showed RON2, RON4, and RON5 form a complex and that RON2 and RON4 reciprocally depend on each other for rhoptry trafficking, whereas RON5 is transported independently.

    Evidence Co-IP from oocyst-derived sporozoite extracts and stage-specific knockdown with invasion assays in P. berghei

    PMID:32817376

    Open questions at the time
    • Molecular basis of the reciprocal RON2/RON4 trafficking dependency not defined
    • Whether the same interdependence operates in merozoites not tested
  12. 2022 High

    Whether RON2 is genuinely required to build a functional entry junction in sporozoites, versus merely present, was unresolved; conditional deletion of RON2 impaired salivary gland colonization and hepatocyte invasion without affecting transcellular migration, and 3D-EM revealed an altered entry junction morphology.

    Evidence DiCre conditional deletion with invasion assays and 3D electron microscopy in P. berghei

    PMID:35731833

    Open questions at the time
    • Structural detail of the sporozoite junction at molecular resolution not defined
    • Host receptor on salivary gland/hepatocyte engaged by the sporozoite RON complex not identified
  13. 2026 High

    The architecture of the full endogenous moving junction and RON2's membrane role were unresolved; cryo-EM of the invasion-stalled complex revealed a 1:1:1:1 AMA1-RON2-RON4-RON5 assembly with two RON2 transmembrane helices anchoring the complex and a RON2/4/5 platform embedding into the RBC membrane, implicating RON2 in host membrane remodeling.

    Evidence Cryo-EM of endogenous complex purified from invasion-stalled P. falciparum with a computationally designed binder

    PMID:42379167

    Open questions at the time
    • Dynamics of membrane insertion and remodeling not directly captured
    • Mechanistic link between the basic platform and internalization force not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved whether RON2 is delivered exclusively into the host membrane from within the erythrocyte or is also exposed on the merozoite surface before invasion, and how these competing observations reconcile with the moving-junction model.
  • Direct visualization of RON2 topology during live invasion lacking
  • Species differences (P. yoelii versus P. falciparum) may confound interpretation
  • Timing of surface exposure relative to host-membrane insertion unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
AMA1 (BINDS RON2 EXTRACELLULAR REGION VIA HYDROPHOBIC GROOVE) [#2, #3, #4, #6]HOST ERYTHROCYTE MEMBRANE (INTEGRAL INSERTION; C-TERMINAL CYSTEINE-RICH DOMAIN BINDS ERYTHROCYTES) [#2, #4, #18]RON3 (PFRON2/3/4 COMPLEX) [#5]RON4 (COMPLEX PARTNER; RECIPROCAL TRAFFICKING DEPENDENCY IN SPOROZOITES) [#0, #15]RON5 (MOVING JUNCTION AND SPOROZOITE COMPLEX PARTNER) [#15, #18]
Complex memberships
Moving junction complex: AMA1-RON2-RON4-RON5 (1:1:1:1) [#0, #18]PfRON2/RON3/RON4 complex distinct from the moving junction [#5]Sporozoite RON2/RON4/RON5 complex [#15]

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 P. falciparum RON2 (PfRON2) localizes to the neck portion of the rhoptry in merozoites, is transcribed at peak levels at the mature schizont stage, and forms a complex with PfRON4 and PfAMA1 as demonstrated by co-immunoprecipitation, establishing conservation of the moving junction complex between T. gondii and P. falciparum. Co-immunoprecipitation studies also showed that PfRON2 is NOT a component of the RhopH complex. Co-immunoprecipitation, immunofluorescence microscopy, transcriptional analysis Parasitology international Medium 18952195
2010 The R1 invasion-inhibitory peptide binds the PfAMA1 hydrophobic trough and prevents PfAMA1 interaction with the PfRON complex (including RON2), placing the AMA1-RON2 interaction after merozoite reorientation and actomyosin motor engagement during the invasion sequence. Peptide-binding assays, invasion inhibition assays, epistasis/temporal ordering by sequential blocking The Journal of biological chemistry Medium 20228060
2011 P. falciparum RON2 is inserted as an integral membrane protein in the host cell membrane during invasion. Using native and recombinant protein interaction assays, the extracellular region of RON2 that binds AMA1 was defined, and invasion inhibition assays confirmed that the RON2-AMA1 interaction is required for P. falciparum merozoite entry into erythrocytes. Integral membrane protein insertion assay, native and recombinant protein interaction assays, invasion inhibition assays PLoS pathogens High 21347343
2011 The RON2 peptide binding site on AMA1 is its hydrophobic pocket. Two conserved, disulfide-linked cysteines in the RON2 peptide are critical residues required for binding to the AMA1 hydrophobic pocket. RON2-AMA1 binding triggers junction formation and commits P. falciparum merozoites to RBC invasion. The RON2 peptide blocked junction formation but, unlike AMA1-specific antibodies targeting the pocket, did not block parasitophorous vacuole formation, indicating junction formation and vacuole formation are molecularly distinct steps. Antibody blocking assays, AMA1 pocket mutants, RON2 peptide competition assays, live microscopy of junction and vacuole formation Proceedings of the National Academy of Sciences of the United States of America High 21788485
2011 The C-terminal cysteine-rich domain of PfRON2 binds host erythrocytes (as shown by COS-7 surface rosetting assay), and both the C-terminal and central cysteine-rich domains of PfRON2 interact with PfAMA1; this binding can be inhibited by mAb 4G2 targeting the AMA1 hydrophobic groove, indicating the hydrophobic groove of PfAMA1 is the binding site for PfRON2. COS-7 surface expression rosetting assay, binding inhibition with monoclonal antibody Parasitology research Medium 22033736
2011 PfRON2 also forms a complex with PfRON3 and PfRON4 (without PfAMA1), as shown by co-immunoprecipitation, constituting a novel RON complex (PfRON2/3/4) distinct from the moving junction complex (PfRON2/4/5/AMA1). Co-immunoprecipitation Parasitology international Low 21237287
2012 Crystal structure of PfAMA1 in complex with a peptide derived from the extracellular region of PfRON2 was determined. The receptor-binding site of PfAMA1 comprises the hydrophobic groove and a region exposed by displacement of the flexible Domain II loop. Mutations of key contact residues in PfRON2 and PfAMA1 abrogate binding between the recombinant proteins. The PfRON2 peptide inhibits P. falciparum erythrocyte invasion, and this inhibitory potency is not affected by AMA1 polymorphisms. The R1 inhibitory peptide mimics the PfRON2 peptide structurally in binding to PfAMA1. X-ray crystallography, site-directed mutagenesis, binding assays, invasion inhibition assay PLoS pathogens High 22737069
2012 In P. falciparum merozoites, RON2 (Rhoptry Neck Protein 2) is released early during invasion, following the junction, as determined by high-definition imaging of endogenously tagged proteins, supporting the model that RON2 is among the first rhoptry neck proteins secreted during invasion. Endogenous gene tagging, high-definition live and fixed fluorescence imaging PloS one Medium 23049965
2013 A small molecule identified by high-throughput screening inhibits P. falciparum merozoite invasion by binding to AMA1 and blocking formation of the AMA1-RON2 complex; electron microscopy confirmed this inhibitor prevents tight junction formation, directly linking AMA1-RON2 complex formation to junction formation during invasion. High-throughput compound screening, binding assay, electron microscopy, invasion inhibition assay Nature communications High 23907321
2015 Live cell imaging with systematic blocking of receptor-ligand interactions established the temporal sequence of invasion: the AMA1-RON2 interaction mediates tight junction formation, which acts as an anchor point for parasite internalization, occurring after the PfRh5-basigin binding step. Live cell imaging, genetic deletion, enzymatic receptor cleavage, inhibitory antibodies and peptides PLoS pathogens High 25723550
2016 The Domain II (DII) loop of PfAMA1 kinetically stabilizes the PfAMA1-RON2 complex by lengthening the complex half-life 18-fold (from ~48 s to ~900 s at 25°C) by slowing the dissociation rate, as determined by fluorescence anisotropy kinetic and thermodynamic measurements comparing wild-type PfAMA1 and a ΔDII-loop engineered construct. Fluorescence anisotropy kinetics, isothermal titration calorimetry, engineered deletion mutant PloS one High 26731670
2009 In P. berghei, RON2 (PBRON2) localizes to the rhoptries in merozoites and is also expressed in sporozoites with the same timing and apical rhoptry location as the known rhoptry protein RAP2/3, establishing RON2 rhoptry localization across both invasion stages. GFP/MYC epitope tagging, fluorescence microscopy, cross-lifecycle expression analysis Molecular and biochemical parasitology Medium 19428669
2014 In P. yoelii sporozoites, RON2 and RON4 are lost following rhoptry discharge during entry into host cells (analogous to merozoite entry), and rhoptry discharge of RON2/RON4 in sporozoites requires the host membrane protein CD81, as sporozoites failed to discharge rhoptries in CD81-negative conditions. Transgenic P. yoelii expressing fluorescent RON2/RON4/RAP2-3, fluorescence microscopy, CD81-dependent entry assay Cellular microbiology Medium 24798694
2018 In P. berghei, RON2 is localized to rhoptries in sporozoites. Sporozoite stage-specific knockdown of ron2 (by promoter swapping to restrict transcription to intraerythrocytic stages) severely impaired sporozoite invasion of mosquito salivary glands by decreasing attachment capacity, and also reduced infectivity to hepatocytes, demonstrating a functional role for RON2 in sporozoite invasion distinct from its role in merozoite invasion. Promoter swapping strategy for stage-specific knockdown, salivary gland invasion assay, hepatocyte infection assay, immunofluorescence Cellular microbiology High 30307699
2019 In P. berghei sporozoites, RON2 localizes to rhoptries (confirmed by immuno-electron microscopy). Unlike merozoites where RON2 and RON4 are neck-restricted, most rhoptry neck proteins including RON2 localize throughout the rhoptries in sporozoites, indicating stage-specific differences in subcompartmentalization. Immuno-electron microscopy, immunofluorescence assay Frontiers in cellular and infection microbiology Medium 31552198
2020 In P. berghei sporozoites, RON2, RON4, and RON5 form a complex (as demonstrated by co-immunoprecipitation from oocyst-derived sporozoite extracts). Stage-specific knockdown revealed that RON2 and RON4 reciprocally affect each other's trafficking to rhoptries in developing sporozoites, while RON5 is independently transported. RON4 and RON5 knockdown reduced sporozoite attachment and salivary gland invasion. Co-immunoprecipitation from sporozoite extracts, sporozoite stage-specific gene knockdown, salivary gland invasion assay, fluorescence microscopy mSphere High 32817376
2022 In P. berghei, conditional DiCre-mediated deletion of RON2 (or RON4) in sporozoites impairs colonization of mosquito salivary glands and invasion of mammalian hepatocytes without affecting transcellular migration. 3D electron microscopy showed that absence of a functional AMA1-RON complex led to altered morphology of the entry junction, associated with epithelial cell damage, establishing that RON2 is required for forming a proper invasion junction in sporozoites. DiCre-mediated conditional gene deletion, mosquito salivary gland invasion assay, hepatocyte invasion assay, 3D electron microscopy PLoS pathogens High 35731833
2021 In P. yoelii merozoites, PyRON2 was already present on the merozoite surface immediately after egress (prior to erythrocyte encounter), and its secretion was not affected by PKAc disruption, in contrast to AMA1. This is inconsistent with the model that RON2 is injected exclusively into the erythrocyte cytosol from within the host, suggesting RON2 may be exposed on the merozoite surface before invasion. DiCre-loxP inducible knockout of PKAc, immunofluorescence microscopy for RON2 localization at egress, erythrocyte invasion assay Parasitology international Medium 34390881
2026 Cryo-EM structure of the endogenous P. falciparum moving junction purified from invasion-stalled parasites revealed a 1:1:1:1 assembly of PfAMA1 with PfRON2, PfRON4, and PfRON5. PfRON2 contains two transmembrane helices that anchor the complex in the red blood cell membrane and display an extracellular handle for PfAMA1 binding. PfAMA1 directly contacts the RBC membrane. PfRON2/4/5 form a large basic platform inside the RBC that electrostatically engages the RBC membrane and embeds amphipathic helices into the bilayer, suggesting RON2 participates in host membrane remodeling during invasion. Cryo-EM structural determination of endogenous complex purified from invasion-stalled P. falciparum, computational protein design of binder Cell High 42379167
2025 Computational simulation of DII loop dynamics in the PfAMA1-PfRON2 complex identified key residues in the PfRON2 helix essential for the post-binding lock conformation. Experimental mutagenesis of these residues validated their functional importance in complex stabilization. Molecular dynamics simulation, mutagenesis with experimental binding validation Chembiochem : a European journal of chemical biology Medium 40067319
2019 For P. vivax RON2, the disulfide bond between C2051 and C2063 in the cyclic form of the PvRON2 peptide is essential for interaction with PvAMA1; the linear peptide lacking this bond showed no detectable interaction by SPR or ITC, establishing that the RON2 disulfide-constrained structure is required for AMA1 binding. Surface plasmon resonance, isothermal titration calorimetry, far western blot, circular dichroism, SAXS Malaria journal High 30683104
2017 Crystal structure of the complex formed between PvAMA1 and PvRON2sp1 peptide was determined. Binding studies showed PvRON2sp1 has strong cross-reactivity with PfAMA1, but PfRON2sp1 has no detectable interaction with PvAMA1; the species asymmetry was largely attributable to PvRON2-Thr2055 versus PfRON2-Arg2041. X-ray crystallography, surface plasmon resonance binding assays PloS one High 28817634
2023 Specific residues in the β-hairpin loop of RON2 and specific residues in AMA1 Loop1E determine species-specific binding between AMA1 and RON2 in P. falciparum and P. vivax. Mutation of specific amino acids in AMA1 Loop1E in P. falciparum ablated RON2 binding without impacting erythrocyte invasion, demonstrating that the AMA1-RON2-loop interaction is NOT essential for invasion and that additional AMA1 interactions are involved. Site-directed mutagenesis of AMA1 and RON2, erythrocyte invasion assay, binding assays Cellular and molecular life sciences : CMLS High 36847896

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 The RON2-AMA1 interaction is a critical step in moving junction-dependent invasion by apicomplexan parasites. PLoS pathogens 270 21347343
2011 Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers commitment to invasion. Proceedings of the National Academy of Sciences of the United States of America 244 21788485
2015 Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes. PLoS pathogens 236 25723550
2010 Interaction between Plasmodium falciparum apical membrane antigen 1 and the rhoptry neck protein complex defines a key step in the erythrocyte invasion process of malaria parasites. The Journal of biological chemistry 213 20228060
2008 Rhoptry neck protein RON2 forms a complex with microneme protein AMA1 in Plasmodium falciparum merozoites. Parasitology international 140 18952195
2012 Structural and functional insights into the malaria parasite moving junction complex. PLoS pathogens 115 22737069
2013 Disrupting malaria parasite AMA1-RON2 interaction with a small molecule prevents erythrocyte invasion. Nature communications 91 23907321
2014 Immunization with a functional protein complex required for erythrocyte invasion protects against lethal malaria. Proceedings of the National Academy of Sciences of the United States of America 79 24958881
2013 Overcoming antigenic diversity by enhancing the immunogenicity of conserved epitopes on the malaria vaccine candidate apical membrane antigen-1. PLoS pathogens 73 24385910
2017 A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection. NPJ vaccines 52 28804644
2017 Antibody profiles to wheat germ cell-free system synthesized Plasmodium falciparum proteins correlate with protection from symptomatic malaria in Uganda. Vaccine 43 28089547
2012 Subcompartmentalisation of proteins in the rhoptries correlates with ordered events of erythrocyte invasion by the blood stage malaria parasite. PloS one 39 23049965
2022 The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts. PLoS pathogens 37 35731833
2011 Plasmodial ortholog of Toxoplasma gondii rhoptry neck protein 3 is localized to the rhoptry body. Parasitology international 34 21237287
2009 Localisation and timing of expression of putative Plasmodium berghei rhoptry proteins in merozoites and sporozoites. Molecular and biochemical parasitology 32 19428669
2015 Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA-RON2 pair. Proceedings of the National Academy of Sciences of the United States of America 29 26712012
2014 Structure and dynamics of apical membrane antigen 1 from Plasmodium falciparum FVO. Biochemistry 29 25360546
2014 CD81 is required for rhoptry discharge during host cell invasion by Plasmodium yoelii sporozoites. Cellular microbiology 28 24798694
2020 Bliss' and Loewe's additive and synergistic effects in Plasmodium falciparum growth inhibition by AMA1-RON2L, RH5, RIPR and CyRPA antibody combinations. Scientific reports 27 32678144
2018 Rhoptry neck protein 2 expressed in Plasmodium sporozoites plays a crucial role during invasion of mosquito salivary glands. Cellular microbiology 27 30307699
2016 Characterization of a novel inhibitory human monoclonal antibody directed against Plasmodium falciparum Apical Membrane Antigen 1. Scientific reports 26 28000709
2011 PvRON2, a new Plasmodium vivax rhoptry neck antigen. Malaria journal 25 21401956
2016 Structure-Activity Studies of β-Hairpin Peptide Inhibitors of the Plasmodium falciparum AMA1-RON2 Interaction. Journal of molecular biology 23 27422009
2023 Structure-based design of a strain transcending AMA1-RON2L malaria vaccine. Nature communications 22 37660103
2017 Cross-reactivity between apical membrane antgen 1 and rhoptry neck protein 2 in P. vivax and P. falciparum: A structural and binding study. PloS one 21 28817634
2016 Stability of the Plasmodium falciparum AMA1-RON2 Complex Is Governed by the Domain II (DII) Loop. PloS one 20 26731670
2015 Crystal structure of Plasmodium knowlesi apical membrane antigen 1 and its complex with an invasion-inhibitory monoclonal antibody. PloS one 18 25886591
2019 Expression and Localization Profiles of Rhoptry Proteins in Plasmodium berghei Sporozoites. Frontiers in cellular and infection microbiology 17 31552198
2015 Computational and biophysical approaches to protein-protein interaction inhibition of Plasmodium falciparum AMA1/RON2 complex. Journal of computer-aided molecular design 16 25822046
2011 The cysteine-rich regions of Plasmodium falciparum RON2 bind with host erythrocyte and AMA1 during merozoite invasion. Parasitology research 16 22033736
2020 Detection of the Rhoptry Neck Protein Complex in Plasmodium Sporozoites and Its Contribution to Sporozoite Invasion of Salivary Glands. mSphere 15 32817376
2023 Defining species-specific and conserved interactions of apical membrane protein 1 during erythrocyte invasion in malaria to inform multi-species vaccines. Cellular and molecular life sciences : CMLS 14 36847896
2015 Isolation of invasive Plasmodium yoelii merozoites with a long half-life to evaluate invasion dynamics and potential invasion inhibitors. Molecular and biochemical parasitology 14 26684675
2018 Receptor-ligand and parasite protein-protein interactions in Plasmodium vivax: Analysing rhoptry neck proteins 2 and 4. Cellular microbiology 13 29488316
2014 Molecular insights into the interaction between Plasmodium falciparum apical membrane antigen 1 and an invasion-inhibitory peptide. PloS one 13 25343578
2013 Natural selection and population genetic structure of domain-I of Plasmodium falciparum apical membrane antigen-1 in India. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 13 23747831
2019 Identification of the Binding Site of Apical Membrane Antigen 1 (AMA1) Inhibitors Using a Paramagnetic Probe. ChemMedChem 12 30653832
2018 The in Vitro Antigenicity of Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2) B- and T-Epitopes Selected by HLA-DRB1 Binding Profile. Frontiers in cellular and infection microbiology 11 29868512
2021 Isolation and light chain shuffling of a Plasmodium falciparum AMA1-specific human monoclonal antibody with growth inhibitory activity. Malaria journal 10 33430886
2022 The direct binding of Plasmodium vivax AMA1 to erythrocytes defines a RON2-independent invasion pathway. Proceedings of the National Academy of Sciences of the United States of America 9 36577076
2019 Structure of Rhoptry Neck Protein 2 is essential for the interaction in vitro with Apical Membrane Antigen 1 in Plasmodium vivax. Malaria journal 9 30683104
2014 Bioinformatic Identification of Peptidomimetic-Based Inhibitors against Plasmodium falciparum Antigen AMA1. Malaria research and treatment 8 25580351
2018 Genetic sequence characterization and naturally acquired immune response to Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2). Malaria journal 7 30382855
2025 A strain-transcending anti-AMA1 human monoclonal antibody neutralizes malaria parasites independent of direct RON2L receptor blockade. Cell reports. Medicine 6 40020675
2024 A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites. Nature communications 6 39174515
2024 Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages. Nature communications 6 39632799
2015 Cheminformatics Based Machine Learning Models for AMA1-RON2 Abrogators for Inhibiting Plasmodium falciparum Erythrocyte Invasion. Molecular informatics 6 27490966
2023 Structure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies. Nature communications 5 37735574
2021 Characterization of AMA1-RON2L complex with native gel electrophoresis and capillary isoelectric focusing. Electrophoresis 5 34679212
2022 A Chimeric Peptide Inhibits Red Blood Cell Invasion by Plasmodium falciparum with Hundredfold Increased Efficacy. Chembiochem : a European journal of chemical biology 4 36449557
2021 Efficient refolding and functional characterization of PfAMA1(DI+DII) expressed in E. coli. Biochemistry and biophysics reports 4 33665380
2020 Application and Comprehensive Analysis of Neighbor Approximated Information Theoretic Configurational Entropy Methods to Protein-Ligand Binding Cases. Journal of chemical theory and computation 4 33190491
2017 Immunization with the Malaria Diversity-Covering Blood-Stage Vaccine Candidate Plasmodium falciparum Apical Membrane Antigen 1 DiCo in Complex with Its Natural Ligand PfRon2 Does Not Improve the In Vitro Efficacy. Frontiers in immunology 4 28702028
2012 Positive diversifying selection on Plasmodium vivax RON2 protein. Parasitology 3 22321319
2024 Conformational variability in the D2 loop of Plasmodium Apical Membrane antigen 1. Journal of structural biology: X 2 39324028
2022 Vesicular stomatitis virus-based vaccine targeting plasmodium blood-stage antigens elicits immune response and protects against malaria with protein booster strategy. Frontiers in microbiology 2 36504817
2025 A Cryptic Loop that Modulates Protein-Protein Interaction: Implications in PfAMA1-PfRON2 Late-stage Binding Event. Chembiochem : a European journal of chemical biology 1 40067319
2021 cAMP-dependent protein kinase regulates secretion of apical membrane antigen 1 (AMA1) in Plasmodium yoelii. Parasitology international 1 34390881
2026 Structural basis for host membrane binding and remodeling by invading malaria parasites. Cell 0 42379167
2025 Chemically Engineered Peptide Efficiently Blocks Malaria Parasite Entry into Red Blood Cells. Biochemistry 0 40062812
2025 Chemical Protein Engineering: Backbone Cyclization Rescues Folding of a 183-Residue Truncated Domain of Malaria Parasite Protein PfAMA1. Chemistry (Weinheim an der Bergstrasse, Germany) 0 40198064
2024 Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages. bioRxiv : the preprint server for biology 0 38370683
2023 Structure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies. Research square 0 37131813