Affinage · Plasmodium

KAHRP

PF3D7_0202000 · knob-associated histidine-rich protein

Annotated
2026-09-07
76 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KAHRP (PF3D7_0202000) is an exported P. falciparum protein essential for assembling knobs on the surface of infected erythrocytes, structures required for cytoadherence of parasitized red cells under physiological shear stress (PMID:9108483). Following co-translational PEXEL processing by plasmepsin V, whose motif position is essential for export (PMID:26832821), KAHRP is trafficked from the parasite endomembrane system through Maurer's clefts into the erythrocyte cytoplasm and finally into knobs, with distinct sequence elements governing individual steps of this pathway (PMID:11598007). At the cytoplasmic face of the host membrane KAHRP self-associates into knob-like structures (PMID:10838226) and assembles in situ as individual modules into ring-shaped units (~60 molecules per knob) that build a spiral scaffold (PMID:31071194, PMID:34514656). This scaffold is anchored to the host spectrin-actin cytoskeleton through direct, domain-mapped interactions: a 72-residue KAHRP fragment binds repeat 4 of α-spectrin (PMID:16006556), a 79-residue segment binds the D3 subdomain of ankyrin R (PMID:24090929), and disrupting either interaction mislocalizes KAHRP to the cytosol, establishing that cytoskeletal attachment governs correct membrane targeting (PMID:16006556, PMID:24090929). KAHRP also directly binds the cytoplasmic domain of PfEMP1 (VARC) with high affinity through its histidine-rich and 5' repeat regions (PMID:10446142, PMID:10838226), forming an electrostatic 'fuzzy complex' (PMID:25726759) whose strength is modulated by erythrocytic casein kinase II phosphorylation of VARC (PMID:19131328). Functionally, the 5' repeat region cross-links to the cytoskeleton to drive knob protrusion and adhesion, while the C-terminal repeat region is critical for functional knob formation and spiral scaffold integrity (PMID:16507777, PMID:31071194); collectively these interactions account for roughly 51% of the increased membrane rigidity of infected red cells (PMID:11807013). KAHRP does not contribute to immobilization of host membrane proteins, indicating its mechanical role is confined to knob assembly (PMID:14615371).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1986 Medium

    Establishing the molecular basis of the knobless phenotype linked KAHRP gene integrity to knob formation, showing that loss of KAHRP expression underlies the knobless state.

    Evidence cDNA cloning, Southern blotting, and chromosomal mapping in knobless P. falciparum mutants

    PMID:3016553

    Open questions at the time
    • Correlational: gene rearrangement linked to phenotype without direct functional rescue
    • Did not define KAHRP molecular function
  2. 1987 Medium

    Sequencing and immunolocalization defined KAHRP's domain architecture and placed the protein physically at knobs, providing the structural foundation for later mechanistic dissection.

    Evidence Gene/protein sequencing plus immunoelectron microscopy with recombinant-protein antibodies

    PMID:3301325 PMID:3313387

    Open questions at the time
    • Function of the histidine-rich and repeat domains not yet tested
    • No binding partners identified
  3. 1997 High

    Targeted disruption resolved whether KAHRP is merely a knob component or is required for the adhesion phenotype, demonstrating it is essential for knob formation and flow-based cytoadherence.

    Evidence Gene knockout with static and flow-based CD36 adhesion assays

    PMID:9108483

    Open questions at the time
    • Did not identify the molecular interactions underlying knob assembly
    • Contribution to membrane mechanics not quantified
  4. 2000 High

    In vitro reconstitution addressed how KAHRP bridges the parasite adhesin to the host skeleton, showing high-affinity binding to the PfEMP1 cytoplasmic domain, self-association into knob-like structures, and binding to spectrin-actin-4.1 complexes.

    Evidence In vitro binding, affinity measurements, self-association and co-sedimentation assays

    PMID:10446142 PMID:10838226

    Open questions at the time
    • In-cell relevance of the mapped binding regions not yet tested
    • Reciprocal binding sites on host proteins not defined
  5. 2001 High

    Live-cell trafficking analysis defined the export route of KAHRP, placing Maurer's clefts as an intermediate depot and mapping sequence elements to individual trafficking steps.

    Evidence GFP fusions, live microscopy, FRAP, and domain deletion analysis

    PMID:11598007

    Open questions at the time
    • Molecular machinery mediating each step not identified
    • PEXEL processing requirement not yet resolved
  6. 2002 High

    Quantitative biophysics answered how much KAHRP contributes to the mechanical stiffening of infected cells, showing it accounts for ~51% of the increased membrane shear modulus.

    Evidence Micropipette aspiration of KAHRP-knockout versus wild-type infected RBCs; competitive flow adhesion assays

    PMID:11807013 PMID:11918556

    Open questions at the time
    • Which molecular interactions produce the rigidity increase not resolved by this assay
  7. 2005 High

    Domain mapping and in-cell perturbation defined KAHRP's spectrin anchor and its export signal, showing the α-spectrin repeat 4 interaction is required for correct membrane localization and that the N-terminal export element can traffic heterologous cargo.

    Evidence Recombinant fragment binding, erythrocyte resealing of competing peptide, immunofluorescence, and GFP chimera trafficking

    PMID:15692070 PMID:16006556

    Open questions at the time
    • Additional cytoskeletal anchors not yet identified
    • Whether spectrin binding drives knob mechanics untested
  8. 2006 High

    Domain-specific transgenic mutants assigned functions to KAHRP's repeat regions, showing the 5' repeats mediate cytoskeletal cross-linking and protrusion while the C-terminal repeats are required for functional knob formation.

    Evidence Transgenic parasites expressing KAHRP domain mutants analyzed by atomic force microscopy, electron microscopy, and flow adhesion

    PMID:16507777

    Open questions at the time
    • Structural basis of C-terminal repeat function not defined
    • Molecular partner of the C-terminal region unknown
  9. 2009 Medium

    Identifying casein kinase II modulation showed the KAHRP-PfEMP1 interaction is regulated by host-cell phosphorylation, linking a signaling input to cytoadherence.

    Evidence In vitro binding with CKII treatment, phosphorylation assay, and cytoadherence to ICAM-1/CSA

    PMID:19131328

    Open questions at the time
    • Physiological trigger controlling CKII activity not defined
    • Effect on knob architecture not measured
  10. 2013 High

    Discovery of the ankyrin R interaction defined a second, KAHRP-specific host anchor required for membrane targeting, distinguishing KAHRP from other exported proteins.

    Evidence In vitro binding, domain mapping to ankyrin D3 subdomain, and erythrocyte D3-loading with immunofluorescence

    PMID:24090929

    Open questions at the time
    • Relative contributions of spectrin versus ankyrin binding to assembly not resolved
    • Order of anchor engagement during assembly untested at this stage
  11. 2015 Medium

    Structural and complex analyses refined the KAHRP-PfEMP1 interaction and placed KAHRP in a knob-associated protein complex, describing an electrostatic fuzzy complex and membership with Hsp40, PfEMP3 and Hsp101.

    Evidence NMR of KAHRP-VARC binding motifs, immunofluorescence co-localization, electron tomography, and co-immunoprecipitation

    PMID:22970262 PMID:25726759 PMID:26637786

    Open questions at the time
    • Co-IP establishes complex membership but not KAHRP's specific role within it
    • Stoichiometry and dynamics of the fuzzy complex in vivo unknown
  12. 2017 Medium

    Preferential spectrin sub-domain mapping refined the architectural model, showing KAHRP repeats associate with β-spectrin domains near the spectrin-ankyrin junction distinct from PfEMP1's preferred α-spectrin site.

    Evidence Biophysical binding assays with structural analysis and computational modeling

    PMID:28806784

    Open questions at the time
    • Model not validated by high-resolution structure of the assembled interface
  13. 2019 High

    High-resolution correlative imaging resolved how KAHRP assembles into knobs, showing in-situ modular assembly into rings over a spiral scaffold that depends on the C-terminal region and host actin remodeling.

    Evidence Correlative STORM-SEM, electron tomography, C-terminal truncation mutants, and cytochalasin D treatment

    PMID:31071194

    Open questions at the time
    • Molecular trigger initiating spiral nucleation not defined
    • Role of actin junction remodeling relative to spectrin/ankyrin anchoring unresolved
  14. 2021 High

    Cryo-EM and single-molecule localization quantified knob composition and captured a shift in KAHRP's host anchoring during assembly, from ankyrin bridges to remnant actin junctions, with ~60 KAHRP molecules per knob.

    Evidence Single-molecule localization microscopy, 35 Å cryo-EM of the spiral scaffold, and a KAHRP-targeting nanoprobe

    PMID:34514656

    Open questions at the time
    • Atomic-resolution structure of KAHRP within the scaffold not yet achieved
    • Mechanism driving the ankyrin-to-actin transition unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution molecular structure of KAHRP within the assembled spiral scaffold, and the mechanism controlling ordered engagement of its multiple host anchors during knob nucleation, remain unresolved.
  • No atomic-resolution structure of KAHRP in situ
  • Order and regulation of spectrin, ankyrin, and actin engagement during assembly not fully defined
  • How PfEMP1 loading is coordinated with scaffold maturation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
ERYTHROCYTE ANKYRIN R (D3 SUBDOMAIN)ERYTHROCYTE Α-SPECTRIN (REPEAT 4)ERYTHROCYTE Β-SPECTRIN (DOMAINS 10–14)ERYTHROCYTIC CASEIN KINASE II (VIA VARC PHOSPHORYLATION)HSP101KAHSP40 (PF3D7_0201800)PFEMP1 CYTOPLASMIC DOMAIN (VARC/VAR_CD)PFEMP3PLASMEPSIN V (PEXEL PROCESSING)SPECTRIN-ACTIN-PROTEIN 4.1 COMPLEX / F-ACTIN
Complex memberships
KAHRP / KAHsp40 (PF3D7_0201800) / PfEMP3 / Hsp101 complexKAHRP–PfEMP1(VARC) fuzzy complexKAHRP–ankyrin R (D3 subdomain) complexKAHRP–α-spectrin repeat 4 complexKnob spiral scaffold (~60 KAHRP molecules per knob)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Targeted gene disruption of KAHRP demonstrated it is essential for knob formation on P. falciparum-infected erythrocytes; knob-negative transfectants showed dramatically reduced binding to CD36 under flow conditions mimicking postcapillary venules, establishing that knobs are required for cytoadherence under physiological shear stress. Targeted gene disruption (knockout), flow-based adhesion assay, static adhesion assay Cell High 9108483
2001 GFP fusions and FRAP experiments demonstrated that KAHRP is trafficked from the parasite endomembrane system through an intermediate depot (Maurer's clefts) between parasite and host, then into the erythrocyte cytoplasm and finally into knobs; sequence elements in KAHRP were identified as essential for individual steps in this pathway, establishing Maurer's clefts as an elaboration of the secretory pathway transposed outside the parasite. GFP fusion constructs, live fluorescence microscopy, FRAP (fluorescence recovery after photobleaching), domain deletion analysis The EMBO journal High 11598007
2002 Micropipette aspiration of infected RBCs from KAHRP-knockout parasites showed KAHRP contributes approximately 51% of the overall increase in membrane shear elastic modulus (rigidity) that occurs in P. falciparum-infected RBCs, a significantly greater contribution than PfEMP3 (~15%). Micropipette aspiration, gene knockout (kahrp deletion), quantitative biophysics Blood High 11807013
1999 Direct binding experiments showed KAHRP interacts with the cytoplasmic domain of PfEMP1 (VARC); three KAHRP fragments were identified that bind VARC, with two high-affinity binding regions mapping to the 63-residue histidine-rich region and the 70-residue 5' repeat region of KAHRP (Kd ~10^-7 M and ~3.3×10^-6 M respectively); deletion of both regions abolished VARC binding. In vitro binding assay (recombinant protein fragments), binding affinity measurements, deletion mutagenesis The Journal of biological chemistry High 10446142
2005 The binding site for spectrin on KAHRP was mapped to a 72-amino-acid fragment (residues 370–441), and the reciprocal KAHRP-binding site on spectrin was localized to repeat 4 of alpha-spectrin (alpha N-5 fragment); resealing of the repeat 4 peptide into erythrocytes mislocalised KAHRP in parasitized cells, establishing that the KAHRP–spectrin interaction is critical for correct membrane localization of KAHRP. In vitro binding assay (recombinant fragments), competition assay, erythrocyte resealing experiment, immunofluorescence The Journal of biological chemistry High 16006556
2006 Expression of mutant KAHRP constructs in transgenic P. falciparum showed that the C-terminal repeat region of KAHRP is critical for formation of functional knobs (assessed by atomic force and electron microscopy); the 5' repeat region of KAHRP is important for cross-linking to the host-cell cytoskeleton, required for knob protrusion and efficient adhesion under physiological flow conditions. Stable transgenic parasite lines expressing KAHRP domain mutants, atomic force microscopy, electron microscopy, flow adhesion assay Blood High 16507777
2000 In vitro binding experiments demonstrated that the cytoplasmic domain of PfEMP1 (VAR_CD) binds to full-length KAHRP with an apparent Kd of ~10.7 nM; KAHRP polypeptides self-associate in solution to form knob-like structures and show binding to spectrin-actin-protein 4.1 complexes; VAR_CD also binds F-actin (Kd ~44.9 nM) and spectrin. In vitro binding assay, affinity measurements, self-association assay, co-sedimentation Molecular and biochemical parasitology High 10838226
2013 KAHRP, but not PfEMP1, PfEMP3, or RESA, binds to erythrocyte ankyrin R; the KAHRP binding site on ankyrin R was mapped to the D3 subdomain of the 89 kDa membrane-binding domain, and the ankyrin-binding segment on KAHRP was localized to a 79-residue sequence; loading erythrocytes with soluble D3 subdomain prevented KAHRP from migrating to the host cell membrane, leaving it diffusely distributed in the cytosol. In vitro binding assay, domain mapping, erythrocyte resealing/loading experiment, immunofluorescence Biochimica et biophysica acta High 24090929
1986 Isolation of cDNA clones for KAHRP showed that in knobless mutants of P. falciparum the KAHRP gene has undergone a chromosomal rearrangement resulting in a deletion in the 3' coding sequence and a telomeric relocation of the truncated gene on chromosome 2, explaining loss of KAHRP mRNA and protein expression and knobless phenotype. cDNA cloning, Southern blotting, chromosomal mapping Nature Medium 3016553
1987 The complete gene sequence of KAHRP was determined; the gene contains a single intron at the 3' boundary of the signal peptide hydrophobic core; the protein contains a histidine-rich region and two separate repeat blocks (5' repeats related to SKKHKDNEDAESVK, and 3' repeats related to SKGATKEAST), both of which bear epitopes recognized by human antibodies during natural infection. cDNA and chromosomal clone sequencing, E. coli expression of repeat domains, human antibody reactivity assay The EMBO journal Medium 3301325
1987 Immunoelectron microscopy using affinity-purified antibodies against recombinant KAHRP established that the protein is clustered on the cytoplasmic side of the erythrocyte membrane and is physically associated with the electron-dense knobs. Immunoelectron microscopy, indirect immunofluorescence, recombinant protein expression in E. coli Proceedings of the National Academy of Sciences of the United States of America Medium 3313387
1992 Stage-specific nuclear run-on analysis demonstrated that KAHRP gene transcription is developmentally regulated during the intraerythrocytic cycle; a sequence motif with two-fold symmetry located 160 bp upstream of the RNA initiation site interacts with parasite nuclear extracts in a stage-specific manner correlating with transcriptional activity of the KAHRP gene. Nuclear run-on analysis, protein-DNA interaction assay (gel shift/footprinting), genomic sequence analysis Nucleic acids research Medium 1620601
2005 The N-terminal protein export element (signal/PEXEL region) of KAHRP, when appended to the transmembrane and C-terminal domains of PfEMP1, was sufficient for efficient trafficking of those domains to the outside of the P. falciparum-infected RBC membrane; the physical state of exported proteins suggested trafficking as a complex rather than in vesicles. GFP chimera constructs, fluorescence microscopy, FRAP Blood Medium 15692070
2016 A mutated KAHRP construct with the PEXEL motif repositioned near the signal sequence was not cleaved by plasmepsin V and was not exported, despite retaining putative PI(3)P-binding residues; restoring the PEXEL to its original position restored processing by plasmepsin V and export, demonstrating that PEXEL position is conserved for co-translational processing and export. Site-directed mutagenesis of KAHRP PEXEL motif, transfection, export assay, biochemical processing analysis Nature communications Medium 26832821
2009 In vitro binding assays showed that VARC phosphorylation by erythrocytic casein kinase II (CKII) alters the binding of VARC to KAHRP; inhibition of CKII reduced cytoadherence of infected RBCs to ICAM-1 and CSA, suggesting KAHRP–VARC interaction is modulated by CKII-mediated phosphorylation. In vitro binding assay, CKII inhibitor/enhancer treatment, phosphorylation assay, cytoadherence assay The Journal of biological chemistry Medium 19131328
2015 Electron tomography of detergent-insoluble skeletons from P. falciparum 3D7 schizonts revealed a highly organized knob skeleton comprising a spiral structure coated by an electron-dense layer; immuno-EM localized KAHRP within these structures, and connections from the knob skeleton to the erythrocyte cytoskeleton were observed. Electron tomography, immuno-electron microscopy, freeze-fracture scanning EM Blood Medium 26637786
2017 Biophysical and structural analyses showed that a repeat region in KAHRP preferentially associates with domains 10–14 of β-spectrin (proximal to the spectrin-ankyrin complex), while the PfEMP1 cytosolic domain interacts broadly with spectrin but shows preference for domain 17 of α-spectrin; structural models combined with prior data suggested a model for knob architecture. Biophysical binding assays, structural analysis, computational modeling PLoS pathogens Medium 28806784
2019 Correlative STORM-SEM showed KAHRP is delivered as individual modules that assemble in situ at the RBC membrane skeleton, giving a ring-shaped fluorescence profile around a dimpled disk visible by SEM; electron tomography revealed a spiral scaffold underlying assembled knobs; truncation of the KAHRP C-terminal region caused loss of ring structures, disruption of raised disks, and aberrant spiral scaffold formation; host cell actin remodeling (blocked by cytochalasin D) was required for knob assembly. Correlative STORM-SEM, electron tomography, KAHRP C-terminal truncation mutants, cytochalasin D treatment, super-resolution microscopy PLoS pathogens High 31071194
2021 Super-resolution microscopy (single-molecule localization) showed KAHRP initially associates with ankyrin bridges in the erythrocyte skeleton but eventually colocalizes with remnant actin junctions; a 35 Å cryo-EM map of the spiral scaffold underlying knobs was obtained and a KAHRP-targeting nanoprobe was shown to bind close to the spiral; approximately 60 KAHRP molecules per knob were detected. Super-resolution single-molecule localization microscopy (SMLM), cryo-electron microscopy, KAHRP nanoprobe, quantitative fluorescence analysis Molecular microbiology High 34514656
2015 Dynamic NMR and binding assays identified four positively charged linear sequence motifs of high intrinsic mobility in KAHRP that interact electrostatically with VARC (cytoplasmic domain of PfEMP1) in solution to form a 'fuzzy complex'; co-localization of KAHRP and VARC to membrane knobs was confirmed by immunofluorescence. NMR spectroscopy, in vitro binding assay, immunofluorescence co-localization Scientific reports Medium 25726759
2012 Co-immunoprecipitation assays demonstrated that KAHRP is in a complex with the parasite Hsp40 (KAHsp40/PF3D7_0201800), PfEMP3, and Hsp101; double IFA showed co-localization of KAHsp40 with KAHRP at the erythrocyte periphery in structures consistent with knobs. Co-immunoprecipitation, immunofluorescence assay (IFA), subcellular fractionation PloS one Medium 22970262
2002 Flow-based adhesion assay using KAHRP-knockout parasite lines showed that loss of KAHRP had a significant effect on the ability of parasitized RBCs to adhere under flow conditions, comparable in impact to loss of PfEMP3 but distinct from loss of RESA or MESA. Competitive flow-based adhesion assay, gene-knockout parasite lines British journal of haematology Medium 11918556
2005 PfTBP (TATA-binding protein) was shown by supershift, footprinting, and chromatin immunoprecipitation assays to associate in vivo with a consensus TATA box sequence located 81 bp upstream of the KAHRP transcription start site, identifying a functional cis-acting element and its trans-acting factor for KAHRP promoter regulation. Supershift assay, DNase I footprinting, chromatin immunoprecipitation (ChIP) Molecular and biochemical parasitology Medium 15760658
1994 Mapping of endonuclease hypersensitive sites in P. falciparum chromatin revealed that spontaneous chromosome breakages within the KAHRP gene coding region occur preferentially within linker regions of nucleosomes with a periodicity of ~155 bp, corresponding to the P. falciparum nucleosome repeat unit, establishing that chromatin structure determines the sites of chromosome breakage. Mapping of endonuclease hypersensitive sites, nucleosome periodicity analysis, pulsed-field gel electrophoresis Nucleic acids research Medium 8065922
2010 In P. berghei, a GFP construct bearing a KAHRP-like N-terminus (signal sequence + PEXEL/VTS motif) was exported into the erythrocyte cytosol, whereas a construct with a PfEMP1-like N-terminus (lacking signal sequence before PEXEL) was not, suggesting proteins with KAHRP-like architecture follow a distinct common export pathway. GFP reporter constructs, P. berghei transfection, fluorescence microscopy PloS one Medium 20419102
2003 Confocal microscopy and FRAP showed that erythrocytes infected with a KAHRP-null parasite strain exhibit the same decrease in lateral mobility of host membrane proteins (band 3, glycophorin) as wild-type infected erythrocytes, indicating KAHRP does not contribute to immobilization of host membrane proteins. Confocal microscopy, FRAP, KAHRP-null parasite line Blood Medium 14615371

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Trafficking and assembly of the cytoadherence complex in Plasmodium falciparum-infected human erythrocytes. The EMBO journal 400 11598007
1990 Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies. Lancet (London, England) 380 1979090
1997 Targeted gene disruption shows that knobs enable malaria-infected red cells to cytoadhere under physiological shear stress. Cell 366 9108483
2002 Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells. Blood 188 11807013
2014 Efficient CRISPR-Cas9-mediated genome editing in Plasmodium falciparum. Nature methods 182 25108687
1984 Knob-positive and knob-negative Plasmodium falciparum differ in expression of a strain-specific malarial antigen on the surface of infected erythrocytes. The Journal of experimental medicine 172 6208311
1995 Natural selection on Plasmodium surface proteins. Molecular and biochemical parasitology 163 7630387
1986 A chromosomal rearrangement in a P. falciparum histidine-rich protein gene is associated with the knobless phenotype. Nature 161 3016553
2006 The role of KAHRP domains in knob formation and cytoadherence of P falciparum-infected human erythrocytes. Blood 126 16507777
1999 Mapping the binding domains involved in the interaction between the Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) and the cytoadherence ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). The Journal of biological chemistry 117 10446142
2005 Trafficking of the major virulence factor to the surface of transfected P. falciparum-infected erythrocytes. Blood 114 15692070
1989 Subtelomeric chromosome deletions in field isolates of Plasmodium falciparum and their relationship to loss of cytoadherence in vitro. Proceedings of the National Academy of Sciences of the United States of America 114 2648403
2000 Plasmodium falciparum erythrocyte membrane protein 1 is anchored to the actin-spectrin junction and knob-associated histidine-rich protein in the erythrocyte skeleton. Molecular and biochemical parasitology 112 10838226
2005 Structural and functional studies of interaction between Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) and erythrocyte spectrin. The Journal of biological chemistry 84 16006556
1987 The complete sequence of the gene for the knob-associated histidine-rich protein from Plasmodium falciparum. The EMBO journal 84 3301325
1987 Primary structure and subcellular localization of the knob-associated histidine-rich protein of Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America 81 3313387
1989 Plasmodium falciparum: cytoadherence of a knobless clone. Experimental parasitology 62 2666153
2004 Common trafficking pathway for variant antigens destined for the surface of the Plasmodium falciparum-infected erythrocyte. Molecular and biochemical parasitology 58 14668007
2016 Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding. Nature communications 57 26832821
1992 A sequence element associated with the Plasmodium falciparum KAHRP gene is the site of developmentally regulated protein-DNA interactions. Nucleic acids research 56 1620601
2012 Structural analysis of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) intracellular domain reveals a conserved interaction epitope. The Journal of biological chemistry 52 22249178
2002 Analysis of transcriptomes of human malaria parasite Plasmodium falciparum using full-length enriched library: identification of novel genes and diverse transcription start sites of messenger RNAs. Gene 49 12095684
2015 A spiral scaffold underlies cytoadherent knobs in Plasmodium falciparum-infected erythrocytes. Blood 43 26637786
2002 Mapping the domains of the cytoadherence ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) that bind to the knob-associated histidine-rich protein (KAHRP). Molecular and biochemical parasitology 43 11755194
2009 Erythrocytic casein kinase II regulates cytoadherence of Plasmodium falciparum-infected red blood cells. The Journal of biological chemistry 41 19131328
2005 Trafficking determinants for PfEMP3 export and assembly under the Plasmodium falciparum-infected red blood cell membrane. Molecular microbiology 40 16262789
1991 In vivo and in vitro derived Palo Alto lines of Plasmodium falciparum are genetically unrelated. Molecular and biochemical parasitology 39 1944415
2012 An exported heat shock protein 40 associates with pathogenesis-related knobs in Plasmodium falciparum infected erythrocytes. PloS one 38 22970262
2002 Assignment of functional roles to parasite proteins in malaria-infected red blood cells by competitive flow-based adhesion assay. British journal of haematology 38 11918556
1994 Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum. Nucleic acids research 38 8065922
2005 Distribution of Plasmodium falciparum genotypes in clinically mild and severe malaria cases in Orissa, India. Transactions of the Royal Society of Tropical Medicine and Hygiene 37 15780346
2013 Interaction of Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) with erythrocyte ankyrin R is required for its attachment to the erythrocyte membrane. Biochimica et biophysica acta 36 24090929
2011 Genetic ablation of a Maurer's cleft protein prevents assembly of the Plasmodium falciparum virulence complex. Molecular microbiology 34 21696460
2005 Recombinant and native Plasmodium falciparum TATA-binding-protein binds to a specific TATA box element in promoter regions. Molecular and biochemical parasitology 32 15760658
2015 The Plasmodium falciparum exportome contains non-canonical PEXEL/HT proteins. Molecular microbiology 31 25850860
2017 Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions. PLoS pathogens 30 28806784
1991 Knobs, knob proteins and cytoadherence in falciparum malaria. The International journal of biochemistry 27 1773882
2003 Plasmodium falciparum induces reorganization of host membrane proteins during intraerythrocytic growth. Blood 26 14615371
2000 The cytoadherence ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) binds to the P. falciparum knob-associated histidine-rich protein (KAHRP) by electrostatic interactions. Molecular and biochemical parasitology 26 11071296
1994 Immunogenicity and antigenicity of a Plasmodium falciparum protein fraction (90-110 kDa) able to protect squirrel monkeys against asexual blood stages. Vaccine 26 8303938
1987 Structure and expression of the knob-associated histidine-rich protein of Plasmodium falciparum. Molecular and biochemical parasitology 26 2448620
2015 Plasmodium falciparum-infected erythrocyte knob density is linked to the PfEMP1 variant expressed. mBio 25 26443460
1997 Erythrocyte membrane alterations in Plasmodium falciparum malaria sequestration. Current opinion in hematology 25 9107533
2019 The knob protein KAHRP assembles into a ring-shaped structure that underpins virulence complex assembly. PLoS pathogens 23 31071194
2000 Plasmodium falciparum: red blood cell binding studies of peptides derived from histidine-rich KAHRP-I, HRP-II and HRP-III proteins. Acta tropica 23 10838219
1994 Transcriptional and nucleosomal characterization of a subtelomeric gene cluster flanking a site of chromosomal rearrangements in Plasmodium falciparum. Nucleic acids research 21 7937144
1988 Genomic organization, structure and possible function of histidine-rich proteins of malaria parasites. The International journal of biochemistry 21 3286310
2021 Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence. PLoS pathogens 20 34614006
2015 Dynamic association of PfEMP1 and KAHRP in knobs mediates cytoadherence during Plasmodium invasion. Scientific reports 20 25726759
2015 A repeat sequence domain of the ring-exported protein-1 of Plasmodium falciparum controls export machinery architecture and virulence protein trafficking. Molecular microbiology 20 26304012
2023 Knobs, Adhesion, and Severe Falciparum Malaria. Tropical medicine and infectious disease 16 37505649
1996 Allelic forms of the knob associated histidine-rich protein gene of Plasmodium falciparum. FEBS letters 16 8603725
2017 Proteome and Structural Organization of the Knob Complex on the Surface of the Plasmodium Infected Red Blood Cell. Proteomics. Clinical applications 15 28981210
2010 Functional evaluation of Plasmodium export signals in Plasmodium berghei suggests multiple modes of protein export. PloS one 15 20419102
1991 Plasmodium falciparum: genetic stability of the Uganda Palo Alto strain propagated in the squirrel monkey (Saimiri sciureus). Experimental parasitology 15 1673101
2016 Infectivity of Plasmodium falciparum in Malaria-Naive Individuals Is Related to Knob Expression and Cytoadherence of the Parasite. Infection and immunity 13 27382019
2014 Targeted disruption of a ring-infected erythrocyte surface antigen (RESA)-like export protein gene in Plasmodium falciparum confers stable chondroitin 4-sulfate cytoadherence capacity. The Journal of biological chemistry 13 25342752
1997 Variations in the C-terminal repeats of the knob-associated histidine-rich protein of Plasmodium falciparum. Biochimica et biophysica acta 13 9128177
2021 KAHRP dynamically relocalizes to remodeled actin junctions and associates with knob spirals in Plasmodium falciparum-infected erythrocytes. Molecular microbiology 12 34514656
1997 Knob proteins in falciparum malaria. The Indian journal of medical research 12 9291676
1988 Expression of the histidine-rich protein PfHRP1 by knob-positive Plasmodium falciparum is not sufficient for cytoadherence of infected erythrocytes. Infection and immunity 11 3053455
2021 Safety, infectivity and immunogenicity of a genetically attenuated blood-stage malaria vaccine. BMC medicine 10 34802442
2018 A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial. Malaria journal 10 30081913
2021 A proteomic glimpse into the effect of antimalarial drugs on Plasmodium falciparum proteome towards highlighting possible therapeutic targets. Pathogens and disease 9 33202000
2011 Tetracysteine-based fluorescent tags to study protein localization and trafficking in Plasmodium falciparum-infected erythrocytes. PloS one 9 21860664
2022 A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections. PLoS computational biology 8 35394995
1987 Knob-associated histidine-rich protein gene. Nature 6 3550477
2011 Genetic polymorphism at the C-terminal domain (region III) of knob-associated histidine-rich protein (KAHRP) of Plasmodium falciparum in isolates from Iran. Parasitology research 4 21594767
1988 Viruslike particles containing knob-associated histidine-rich protein are secreted into the culture medium of Plasmodium falciparum in vitro cultures. Biochemical and biophysical research communications 4 3279953
2025 Pair cross-correlation analysis for assessing protein co-localization. Biophysical journal 2 40077967
2025 Deep learning image analysis for continuous single-cell imaging of dynamic processes in Plasmodium falciparum-infected erythrocytes. Communications biology 1 40133663
2018 Genetic diversity at the C-terminal domain of knob-associated histidine-rich protein (KAHRP) of Plasmodium falciparum isolates from Burundi, Eastern Africa. Annals of medicine and surgery (2012) 1 30191063
2018 Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins. Scientific reports 1 30279439
2025 Nucleotide-resolution Mapping of RNA N6-Methyladenosine (m6A) modifications and comprehensive analysis of global polyadenylation events in mRNA 3' end processing in malaria pathogen Plasmodium falciparum. bioRxiv : the preprint server for biology 0 39829786
2022 Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi Arabia. Journal of tropical medicine 0 35387278
2000 Plasmodium falciparum: polymorphism in regions II and III of the knob-associated histidine-rich protein gene from two areas of different endemicity. Experimental parasitology 0 10831395