Affinage · Plasmodium

RH5

PF3D7_0424100 · reticulocyte binding protein homologue 5

Annotated
2026-09-07
99 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RH5 (PF3D7_0424100) is an essential, rhoptry-localized merozoite ligand of P. falciparum that mediates a universally required step of erythrocyte invasion by engaging the host receptor basigin (PMID:19000690, PMID:22080952). RH5 is unusual among the PfRh family in lacking transmembrane and cytosolic regions (PMID:19000690); it adopts a novel kite-shaped fold of nine mostly anti-parallel α-helices encasing an N-terminal β-hairpin, presenting the basigin-binding surface and inhibitory-antibody epitopes at one tip (PMID:25296023, PMID:25132548). RH5 binding to basigin is essential and strain-transcending, established by soluble-basigin and antibody blockade, a low-affinity natural Ok(a−) variant, and CRISPR knockout of basigin that abolishes invasion by all tested strains (PMID:22080952, PMID:29078358). This interaction is a molecular determinant of host tropism: RH5 binds human basigin with high affinity but chimpanzee basigin weakly and gorilla basigin not at all, and a single residue acquired after zoonotic transfer restricted the ancestral broadly-binding RH5 to human basigin (PMID:24297912, PMID:31613878). Functionally, the RH5–basigin engagement triggers a Ca²⁺ signal in the erythrocyte with cytoskeletal phosphorylation changes, produces a transient pore/opening at the merozoite–erythrocyte interface, and acts after strong deformation but before AMA1-RON2 tight-junction formation (PMID:25723550, PMID:27374406, PMID:28409866). RH5 does not function alone: it assembles with PfRipr and the GPI-anchored CyRPA into a surface-tethered RCR complex, which is further bound by a disulfide-linked PfPTRAMP–PfCSS pair to form the pentameric PCRCR complex that anchors merozoite–erythrocyte membrane contact (PMID:21909261, PMID:25583518, PMID:30542156, PMID:36396942, PMID:38123677). Prior to invasion RH5 is anchored to the merozoite surface via its cleaved conserved N-terminal region binding the surface protein P113 (PMID:28186186). RH5 defines a Laverania-specific invasion mechanism, being absent from P. knowlesi and P. vivax where CyRPA and RIPR act in distinct complexes (PMID:31185066). Neutralizing anti-RH5 antibodies that block basigin binding are a mechanistic correlate of protection in vivo, and a class of non-neutralizing 'invasion-slowing' antibodies potentiates them (PMID:24293631, PMID:31204103, PMID:31028254).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2008 High

    Establishing RH5 as an essential apical merozoite ligand answered whether this atypical PfRh member participates in invasion at all and where it acts.

    Evidence Immunofluorescence rhoptry localization, inhibitory immune serum in invasion assays, and essentiality assessment in P. falciparum; genetic cross and allelic replacement linking RH5 polymorphisms to host erythrocyte range

    PMID:18621009 PMID:19000690

    Open questions at the time
    • Erythrocyte receptor not yet identified
    • Molecular basis of the polymorphism-driven binding change unresolved
  2. 2011 High

    Identifying basigin as the RH5 receptor and PfRipr as a binding partner answered what host molecule RH5 engages and revealed that RH5 acts within a parasite complex.

    Evidence AVEXIS library screen, SPR, basigin knockdown/antibody blockade and Ok(a−) invasion assays; ion-exchange/IP-MS identifying the RH5–PfRipr complex with distinct organellar origins in P. falciparum

    PMID:21909261 PMID:22080952

    Open questions at the time
    • How the complex is tethered to the membrane-anchorless RH5 unknown
    • Downstream signalling consequence of binding not defined
  3. 2013 High

    Quantifying RH5 affinity for basigin across great-ape species and mapping the receptor-binding region tied the RH5–basigin interaction to P. falciparum host restriction and located the binding determinants.

    Evidence Recombinant binding assays with human/chimp/gorilla basigin plus basigin mutagenesis; allelic replacement at multiple RH5 codons scoring primate/rodent invasion; anti-RH5 vaccine antibody blocking and mAb epitope mapping in P. falciparum

    PMID:23305874 PMID:24293631 PMID:24297912

    Open questions at the time
    • Structural basis of binding not yet solved
    • In-parasite role of specific residues on human basigin binding indirect
  4. 2014 High

    Solving the RH5 fold and its complex with basigin and inhibitory antibodies answered how RH5 is built and how it engages receptor and is neutralized.

    Evidence X-ray crystallography of RH5 alone (2.18 Å) and co-crystals of RH5 with basigin and inhibitory Fabs from P. falciparum 3D7 and other isolates

    PMID:25132548 PMID:25296023

    Open questions at the time
    • Structure of the full multiprotein complex not resolved
    • Mechanism linking binding to downstream invasion steps unknown
  5. 2015 High

    Defining the trimeric RH5–PfRipr–CyRPA complex and placing the RH5–basigin step in the invasion sequence answered how the anchorless RH5 is surface-tethered and what its engagement accomplishes mechanically.

    Evidence Reciprocal co-IP with GPI-anchor verification of CyRPA; live-cell imaging with staged receptor-ligand blockade defining pore formation after deformation and before tight junction in P. falciparum

    PMID:25583518 PMID:25723550

    Open questions at the time
    • Molecular nature of the pore unresolved
    • Signalling trigger downstream of pore not identified
  6. 2016 High

    Conditional loss-of-function and junctional colocalization tied the RCR complex to Ca²⁺ release and tight-junction formation, establishing its indispensability at the invasion interface.

    Evidence TetR-DOZI conditional knockdown of PfRipr/CyRPA, super-resolution colocalization with RH5, and Ca²⁺ signalling assays in P. falciparum

    PMID:27374406

    Open questions at the time
    • Direct mechanistic link from RH5–basigin binding to Ca²⁺ release not fully dissected
  7. 2017 Medium

    Identifying the RH5 N-terminus–P113 interaction and showing RH5–basigin alone triggers erythrocyte Ca²⁺ signalling answered how RH5 is pre-anchored and confirmed its receptor engagement is a host-signalling event; CRISPR basigin knockout cemented the interaction's universal essentiality.

    Evidence AVEXIS interaction mapping of RH5Nt–P113; erythrocyte Ca²⁺ fluorescence and cytoskeletal phosphoproteomics with anti-RH5 blockade; CRISPR/Cas9 basigin knockout in JK-1 cells across strains (P. falciparum)

    PMID:28186186 PMID:28409866 PMID:29078358

    Open questions at the time
    • RH5Nt–P113 interaction lacks in-parasite genetic validation in the timeline
    • Ca²⁺ signalling pathway components in erythrocyte not identified
  8. 2018 High

    The cryo-EM RCR structure answered how CyRPA assembles the complex and proposed that RH5 and Ripr insert into the host membrane, refining the invasion mechanism.

    Evidence Cryo-EM at subnanometre resolution, JK-1 erythrocyte binding assays, and high-molecular-weight membrane-insertion analysis in P. falciparum

    PMID:30542156

    Open questions at the time
    • Membrane-insertion model later challenged
    • Full pentameric assembly not yet captured
  9. 2019 High

    Functional dissection of anti-RH5 antibodies and species-comparative and ancestral-resurrection work established RH5-neutralizing antibody as a correlate of protection, defined a potentiator antibody class, and traced host-specificity evolution to a single residue.

    Evidence Passive transfer of Fc-null neutralizing vs non-neutralizing mAbs in Aotus; human mAb panels with live-imaging invasion-speed and GIA assays; conditional knockdown/co-IP in P. knowlesi and P. vivax; ancestral RH5 resurrection with SPR/AVEXIS and mutagenesis

    PMID:31028254 PMID:31185066 PMID:31204103 PMID:31613878

    Open questions at the time
    • Mechanism of invasion-slowing potentiation at molecular level not fully defined
    • Species-divergence findings rest on single-lab comparative data
  10. 2022 High

    Discovery of the pentameric PCRCR complex answered how the RCR complex is connected to the merozoite membrane and defined its role in anchoring membrane contact.

    Evidence Conditional knockouts of PfPTRAMP and PfCSS, invasion-inhibitory nanobodies, lattice light-sheet microscopy, and cryo-EM of nanobody–PfCSS complexes in P. falciparum

    PMID:36396942

    Open questions at the time
    • Full-length assembled PCRCR structure not solved in this study
    • Precise geometry of RH5 within the pentamer during contact unresolved
  11. 2023 High

    The cryo-EM PfRCR structure revised the invasion model, showing a disulfide-locked rigid RH5 can still mediate invasion, arguing against RH5 membrane-insertion via conformational opening.

    Evidence Cryo-EM of the RH5–CyRPA–RIPR complex, disulfide-locked RH5 functional invasion assays, and PCRCR modelling in P. falciparum

    PMID:38123677

    Open questions at the time
    • Exact molecular event coupling RH5 receptor binding to pore/signalling still not defined
    • Structure of the fully assembled membrane-engaged pentamer not captured

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RH5–basigin engagement is mechanistically transduced into erythrocyte Ca²⁺ release, cytoskeletal remodelling, and pore formation remains the central unresolved question.
  • No molecular identity for the transient pore
  • Host signalling machinery downstream of RH5 binding unidentified
  • In-parasite validation of RH5Nt–P113 anchoring not reported in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
BASIGIN / CD147 (OK BLOOD GROUP) — ERYTHROCYTE RECEPTOR [#2, #4, #17, #21]CYRPA (GPI-ANCHORED COMPLEX TETHER) [#7, #13, #19]P113 (MEROZOITE SURFACE ANCHOR FOR RH5 N-TERMINUS) [#10]PFCSS [#18, #19]PFPTRAMP [#18, #19]PFRIPR [#3, #13, #19]
Complex memberships
PfPTRAMP–PfCSS–RH5–CyRPA–PfRipr pentameric PCRCR complex [#18, #19]RH5–CyRPA–PfRipr (RCR) trimeric complex [#7, #13, #19]RH5–PfRipr complex [#3]

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 RH5 (PF3D7_0424100) is expressed as a 63 kDa protein localized at the apical end (rhoptries) of P. falciparum merozoites, binds to a glycosylated receptor on the erythrocyte surface, and is essential for erythrocyte invasion; rabbit immune serum raised against its ecto-domain inhibits parasite invasion in vitro. RH5 lacks a transmembrane and cytosolic region, distinguishing it from other PfRh family members. Immunofluorescence localization, in vitro invasion inhibition assay with immune serum, genetic essentiality assessment International journal for parasitology High 19000690
2008 Polymorphisms in RH5 at specific residues (including position 204) determine whether P. falciparum can invade Aotus nancymaae erythrocytes; a proteolytic fragment of RH5 from infective parasites bound to A. nancymaae erythrocytes, establishing RH5 as a parasite ligand whose binding domain can be altered by amino acid substitutions to recognize different host erythrocyte surface receptors. Genetic cross linkage analysis, allelic replacement, erythrocyte binding assay with proteolytic RH5 fragment Cell host & microbe High 18621009
2011 Basigin (Ok blood group antigen, CD147) is the erythrocyte receptor for RH5. Soluble basigin or anti-basigin antibodies potently block erythrocyte invasion by all tested P. falciparum strains. Ok(a−) erythrocytes expressing a basigin variant with lower affinity for RH5 show reduced invasion efficiency, establishing the RH5–basigin interaction as essential and universally required across strains. Systematic library screen of erythrocyte proteins (AVEXIS), surface plasmon resonance binding assay, basigin knockdown, blocking with soluble basigin and antibodies, Ok(a−) erythrocyte invasion assay Nature High 22080952
2011 RH5 forms a complex with PfRipr (PFC1045c), a novel cysteine-rich EGF-domain-containing protein, in merozoites. RH5 is contained within rhoptries while PfRipr localises to micronemes; both are released during invasion and form a complex shed into culture supernatant. Antibodies against PfRipr potently inhibit merozoite attachment and invasion, indicating the RH5–PfRipr complex is essential for invasion. Ion-exchange chromatography, immunoprecipitation, mass spectrometry, immunofluorescence localization, in vitro invasion inhibition assay PLoS pathogens High 21909261
2013 P. falciparum RH5 binds human basigin with high affinity but binds chimpanzee basigin with significantly lower affinity and does not bind gorilla basigin, mirroring the known host tropism of P. falciparum. Site-directed mutagenesis of basigin residues identified specific residues responsible for species specificity of RH5 binding, establishing the RH5–basigin interaction as a molecular determinant of P. falciparum host restriction to humans. Recombinant protein production, biophysical binding assays (SPR/AVEXIS), site-directed mutagenesis of basigin Proceedings of the National Academy of Sciences of the United States of America High 24297912
2014 Crystal structure of RH5 (PF3D7_0424100) was determined at 2.18 Å resolution. RH5 adopts a novel fold comprising nine mostly anti-parallel α-helices encasing an N-terminal β-hairpin, with an overall elliptical disk shape. This is the first 3D structure of the PfRh protein family. X-ray crystallography (2.18 Å resolution) eLife High 25296023
2014 Crystal structures of RH5 in complex with basigin and two distinct inhibitory antibodies were determined. RH5 adopts a kite-like architecture in which two three-helical bundles present binding sites for basigin and for inhibitory antibodies at one tip, defining the structural basis of receptor engagement and antibody neutralization. X-ray crystallography of RH5–basigin co-crystal and RH5–antibody Fab co-crystals Nature High 25132548
2015 RH5 forms a multiprotein complex (PfRH5/PfRipr/CyRPA) on the merozoite surface. CyRPA is a GPI-anchored protein that tethers the complex to the merozoite surface (since neither RH5 nor PfRipr have transmembrane domains or GPI anchors). Antibodies against each component co-immunoprecipitated the intact complex. CyRPA localizes to micronemes. Antibodies against CyRPA display potent strain-transcending invasion inhibition, and combined RH5 + CyRPA antibodies show synergistic invasion inhibition. Co-immunoprecipitation, GPI-anchor verification (PI-PLC treatment), immunofluorescence localization, in vitro invasion inhibition assay Proceedings of the National Academy of Sciences of the United States of America High 25583518
2015 The RH5–basigin binding step during invasion results in the formation of a pore or opening between the parasite and host cell, through which small molecules and possibly invasion components can flow. This step occurs after EBA/PfRh ligand-mediated strong erythrocyte deformation and before AMA1-RON2-mediated tight junction formation. Live cell imaging of invasion with systematic blockade of individual receptor-ligand pairs (genetic deletion, enzymatic treatment, inhibitory antibodies/peptides/small molecules) PLoS pathogens High 25723550
2016 Conditional loss of function of PfRipr or CyRPA blocks P. falciparum erythrocyte invasion; super-resolution microscopy revealed that PfRipr, CyRPA, and RH5 colocalize at the junction between merozoites and erythrocytes during invasion. The RH5/PfRipr/CyRPA complex is required for triggering Ca²⁺ release and establishing the tight junction. Conditional knockdown lines (TetR-DOZI system), super-resolution microscopy, Ca²⁺ signaling assay Cell host & microbe High 27374406
2017 P113, a merozoite surface protein, directly interacts with the conserved N-terminal region of RH5 (RH5Nt). This RH5Nt–P113 interaction provides a releasable anchoring mechanism for RH5 to the merozoite surface prior to invasion. The N-terminal region is cleaved from the native protein during processing. Recombinant protein production, AVEXIS protein interaction assay, binding interdependency mapping of RH5 complex components Nature communications Medium 28186186
2017 RH5–basigin interaction on its own triggers a Ca²⁺ signal in the erythrocyte, leading to phosphorylation changes in RBC cytoskeletal proteins and overall alterations in RBC cytoskeleton architecture. Antibodies blocking RH5 prevent this Ca²⁺ signal and invasion before tight junction formation. Ca²⁺ fluorescence assay in erythrocytes, phosphoproteomic analysis of RBC cytoskeletal proteins, invasion inhibition assay with anti-RH5 antibodies Cellular microbiology Medium 28409866
2013 Vaccine-induced polyclonal anti-RH5 antibodies inhibit tight attachment of merozoites to erythrocytes and block the RH5–basigin interaction. Monoclonal antibody analysis showed: (1) blocking the RH5–basigin interaction in vitro is predictive of functional neutralization; (2) neutralizing mAbs bind spatially related epitopes involving at least two defined regions of RH5 primary sequence; (3) intact bivalent IgG contributes to but is not necessary for parasite neutralization. In vitro invasion inhibition assay, ELISA-based RH5–basigin blocking assay, monoclonal antibody epitope mapping Journal of immunology Medium 24293631
2018 Cryo-EM structure of the trimeric Rh5–CyRPA–Ripr (RCR) complex was determined at subnanometre resolution. CyRPA is a critical mediator of complex assembly with blades 4–6 of its β-propeller forming contact sites for both Rh5 and Ripr. The complex binds erythrocyte cell line JK-1 significantly better than Rh5 alone, and this binding occurs through insertion of Rh5 and Ripr into host membranes as a high-molecular-weight complex. Comparison with the Rh5–basigin crystal structure suggests Rh5 and Ripr are positioned parallel to the erythrocyte membrane before membrane insertion. Cryo-electron microscopy (subnanometre resolution), erythrocyte binding assay, high-molecular-weight complex membrane insertion analysis Nature High 30542156
2019 A subset of human anti-RH5 monoclonal antibodies that are non-neutralizing reduce the speed of red blood cell invasion by the merozoite (slowing invasion without blocking it), and these 'invasion-slowing' antibodies potentiate the effect of all neutralizing RH5 antibodies as well as synergize with antibodies targeting other malaria invasion proteins. Neutralizing mAbs bind three distinct sites on RH5. Human mAb isolation from vaccinees, live-imaging invasion speed assay, in vitro growth inhibition assay, epitope mapping Cell High 31204103
2019 Using passive transfer of neutralizing (c2AC7) versus non-neutralizing (c4BA7) anti-RH5 chimeric monoclonal antibodies with Fc mutations eliminating complement and FcR engagement into Aotus nancymaae monkeys challenged with P. falciparum, the neutralizing RH5-binding mAb conferred complete protection (6/6 animals) whereas non-neutralizing RH5-binding mAb conferred no protection (0/6), establishing that merozoite-neutralizing antibody against RH5 is a mechanistic correlate of protection. Passive transfer of engineered chimeric mAbs, P. falciparum blood-stage challenge in Aotus monkeys Nature communications High 31028254
2019 RH5 is restricted to the Laverania subgenus (including P. falciparum) and is absent in non-Laverania species such as P. knowlesi and P. vivax. In P. knowlesi, CyRPA and RIPR are each essential for erythrocyte invasion but neither forms a complex with each other nor with an RH5-like molecule (PkRIPR is part of a different trimeric complex; PkCyRPA functions without other parasite binding partners), demonstrating that RH5 defines a distinct invasion mechanism specific to Laverania. Conditional knockdown in P. knowlesi and P. vivax, co-immunoprecipitation to assess complex formation PLoS pathogens Medium 31185066
2019 The ancestral introgressed RH5 sequence (resurrected computationally and expressed recombinantly) bound basigin from both humans and gorillas, whereas current P. falciparum RH5 binds only human basigin. A single amino acid mutation in RH5 is responsible for the subsequent restriction to human basigin specificity after the zoonotic transfer. Ancestral sequence resurrection, recombinant protein expression, quantitative protein interaction assays (SPR/AVEXIS), site-directed mutagenesis PLoS biology High 31613878
2022 RH5, CyRPA, and RIPR (RCR complex) are bound by a heteromeric disulfide-linked PfPTRAMP–PfCSS complex to form a pentameric PCRCR complex. Conditional knockouts of PfPTRAMP and PfCSS, invasion inhibitory nanobodies against both, and lattice light-sheet microscopy show these components are essential for merozoite invasion. The PCRCR complex functions to anchor contact between merozoite and erythrocyte membranes brought together by parasite deformations. Conditional knockout (P. falciparum), nanobody invasion inhibition, lattice light-sheet microscopy, cryo-EM structure of nanobody–PfCSS complexes Nature microbiology High 36396942
2023 Cryo-EM structure of the PfRCR complex (RH5–CyRPA–RIPR) was determined, showing that RIPR consists of an ordered multidomain core flexibly linked to an elongated tail. The elongated tail of RIPR binds to the PfCSS–PfPTRAMP complex on the parasite membrane, while the structured core presents CyRPA and RH5 to erythrocyte receptors. RH5 with a rigid, disulfide-locked conformation can mediate efficient erythrocyte invasion, arguing against the previous model of RH5 opening to insert into the membrane. CyRPA-binding antibodies neutralize invasion through a steric mechanism. Cryo-EM structure determination, disulfide-locked RH5 functional assay, erythrocyte binding assay, modelling of PCRCR complex Nature High 38123677
2013 Various RH5 allelic polymorphisms at positions 204, 347, 358, 362, 410, and 429 introduced by allelic replacement into the non-virulent 7G8 P. falciparum line determine invasion competence into A. nancymaae and rat erythrocytes; polymorphisms at position 204 (204K or 204R) also confer rat erythrocyte invasion with differential neuraminidase sensitivity, defining the RH5 receptor-binding domain region. Allelic replacement mutagenesis, invasion assays into primate and rodent erythrocytes, neuraminidase treatment Molecular and biochemical parasitology High 23305874
2017 CRISPR/Cas9 knockout of basigin (BSG) in JK-1 erythroleukemia-derived RBCs completely blocks P. falciparum invasion in a strain-transcendent manner, confirming the essential and universal role of the BSG–RH5 interaction for erythrocyte invasion across all tested strains. CRISPR/Cas9 gene knockout in immortal JK-1 erythroleukemia line, multi-strain P. falciparum invasion assay Proceedings of the National Academy of Sciences of the United States of America High 29078358

Source papers

Stage 0 corpus · 99 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature 528 22080952
2015 Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes. PLoS pathogens 236 25723550
2011 The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. Nature communications 229 22186897
2008 Reticulocyte-binding protein homologue 5 - an essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum. International journal for parasitology 208 19000690
2008 Erythrocyte binding protein PfRH5 polymorphisms determine species-specific pathways of Plasmodium falciparum invasion. Cell host & microbe 205 18621009
2014 Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies. Nature 184 25132548
2015 A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in aotus monkeys. Cell host & microbe 178 25590760
2016 Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium falciparum Invasion of Erythrocytes. Cell host & microbe 163 27374406
2015 Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion. Proceedings of the National Academy of Sciences of the United States of America 144 25583518
2014 Plasmodium falciparum erythrocyte invasion: combining function with immune evasion. PLoS pathogens 131 24651270
2011 An EGF-like protein forms a complex with PfRh5 and is required for invasion of human erythrocytes by Plasmodium falciparum. PLoS pathogens 131 21909261
2019 Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies. Cell 124 31204103
2013 Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5. Journal of immunology (Baltimore, Md. : 1950) 123 24293631
2021 Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination. Med (New York, N.Y.) 118 34223402
2012 A full-length recombinant Plasmodium falciparum PfRH5 protein induces inhibitory antibodies that are effective across common PfRH5 genetic variants. Vaccine 115 23146673
2012 Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens. PLoS pathogens 112 23144611
2017 Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions. JCI insight 110 29093263
2013 Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria. The Journal of infectious diseases 100 24133188
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
2015 Recent advances in recombinant protein-based malaria vaccines. Vaccine 92 26458807
2018 Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex. Nature 84 30542156
2008 PfRH5: a novel reticulocyte-binding family homolog of plasmodium falciparum that binds to the erythrocyte, and an investigation of its receptor. PloS one 79 18827878
2017 One-step design of a stable variant of the malaria invasion protein RH5 for use as a vaccine immunogen. Proceedings of the National Academy of Sciences of the United States of America 73 28096331
2013 Bacterially expressed full-length recombinant Plasmodium falciparum RH5 protein binds erythrocytes and elicits potent strain-transcending parasite-neutralizing antibodies. Infection and immunity 70 24126527
2015 Host-parasite interactions that guide red blood cell invasion by malaria parasites. Current opinion in hematology 63 25767956
2017 P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5. Nature communications 59 28186186
2017 Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody. eLife 59 28195038
2014 Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes. eLife 59 25296023
2010 Erythrocyte invasion and merozoite ligand gene expression in severe and mild Plasmodium falciparum malaria. The Journal of infectious diseases 59 20050806
2022 PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum. Nature microbiology 58 36396942
2019 A defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates. Nature communications 58 31028254
2018 Production, quality control, stability, and potency of cGMP-produced Plasmodium falciparum RH5.1 protein vaccine expressed in Drosophila S2 cells. NPJ vaccines 58 30131879
2013 Plasmodium falciparum merozoite surface antigen, PfRH5, elicits detectable levels of invasion-inhibiting antibodies in humans. The Journal of infectious diseases 56 23904294
2020 The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target. Trends in parasitology 55 32359873
2017 Accelerating the clinical development of protein-based vaccines for malaria by efficient purification using a four amino acid C-terminal 'C-tag'. International journal for parasitology 55 28153778
2021 Human Basigin (CD147) Does Not Directly Interact with SARS-CoV-2 Spike Glycoprotein. mSphere 54 34378982
2017 Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA. eLife 53 28195530
2017 CRISPR/Cas9 knockouts reveal genetic interaction between strain-transcendent erythrocyte determinants of Plasmodium falciparum invasion. Proceedings of the National Academy of Sciences of the United States of America 53 29078358
2015 Basigin is a druggable target for host-oriented antimalarial interventions. The Journal of experimental medicine 53 26195724
2016 The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria. Scientific reports 52 27604417
2019 Antibody responses to merozoite antigens after natural Plasmodium falciparum infection: kinetics and longevity in absence of re-exposure. BMC medicine 51 30696449
2016 Production of full-length soluble Plasmodium falciparum RH5 protein vaccine using a Drosophila melanogaster Schneider 2 stable cell line system. Scientific reports 50 27457156
2015 Structurally conserved erythrocyte-binding domain in Plasmodium provides a versatile scaffold for alternate receptor engagement. Proceedings of the National Academy of Sciences of the United States of America 49 26715754
2015 A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. PLoS neglected tropical diseases 48 26701602
2014 A malaria vaccine candidate based on an epitope of the Plasmodium falciparum RH5 protein. Malaria journal 48 25135070
2019 Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes. Cellular microbiology 47 30965383
2015 Progress with viral vectored malaria vaccines: A multi-stage approach involving "unnatural immunity". Vaccine 45 26476366
2021 Protein/AS01B vaccination elicits stronger, more Th2-skewed antigen-specific human T follicular helper cell responses than heterologous viral vectors. Cell reports. Medicine 43 33763653
2022 Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens. PLoS computational biology 42 35108259
2014 Association of antibodies to Plasmodium falciparum reticulocyte binding protein homolog 5 with protection from clinical malaria. Frontiers in microbiology 41 25071730
2019 Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. PLoS pathogens 40 31185066
2019 Functional Comparison of Blood-Stage Plasmodium falciparum Malaria Vaccine Candidate Antigens. Frontiers in immunology 38 31214195
2015 Variation in Plasmodium falciparum erythrocyte invasion phenotypes and merozoite ligand gene expression across different populations in areas of malaria endemicity. Infection and immunity 37 25870227
2024 Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial. The Lancet. Infectious diseases 36 38880111
2019 Resurrection of the ancestral RH5 invasion ligand provides a molecular explanation for the origin of P. falciparum malaria in humans. PLoS biology 36 31613878
2017 P. falciparum RH5-Basigin interaction induces changes in the cytoskeleton of the host RBC. Cellular microbiology 36 28409866
2012 Targeting sialic acid dependent and independent pathways of invasion in Plasmodium falciparum. PloS one 35 22253925
2015 Analysis of Erythrocyte Invasion Mechanisms of Plasmodium falciparum Clinical Isolates Across 3 Malaria-Endemic Areas in Ghana. The Journal of infectious diseases 34 25838264
2018 Kinetics of antibody responses to PfRH5-complex antigens in Ghanaian children with Plasmodium falciparum malaria. PloS one 33 29883485
2013 Identifying novel Plasmodium falciparum erythrocyte invasion receptors using systematic extracellular protein interaction screens. Cellular microbiology 33 23617720
2023 The PfRCR complex bridges malaria parasite and erythrocyte during invasion. Nature 32 38123677
2016 Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate. Vaccine 32 27692771
2013 Analyses of interactions between heparin and the apical surface proteins of Plasmodium falciparum. Scientific reports 32 24212193
2012 Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru. Malaria journal 32 23110555
2024 Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children. The Lancet. Infectious diseases 31 39672183
2023 Superior antibody immunogenicity of a viral-vectored RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults. Med (New York, N.Y.) 29 37572659
2012 Basigin: a multifunctional membrane protein with an emerging role in infections by malaria parasites. Expert opinion on therapeutic targets 29 22880881
2024 Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex. Nature communications 27 38849365
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
2013 Various PfRH5 polymorphisms can support Plasmodium falciparum invasion into the erythrocytes of owl monkeys and rats. Molecular and biochemical parasitology 27 23305874
2024 Vaccines and monoclonal antibodies: new tools for malaria control. Clinical microbiology reviews 26 38656211
2020 Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A. Scientific reports 26 32313230
2018 KILchip v1.0: A Novel Plasmodium falciparum Merozoite Protein Microarray to Facilitate Malaria Vaccine Candidate Prioritization. Frontiers in immunology 26 30619257
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2026 Serological evidence of continued exposure to Plasmodium falciparum among residents in a near-elimination setting. Frontiers in microbiology 0 41586363
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