PF3D7_0100300
erythrocyte membrane protein 1, PfEMP1
Audit flag: literature coverage
- Annotated
- 2026-09-11
100 papers in source corpus
Shared family summary
var gene family (PfEMP1), all members · written from 190 papers across 65 member genes
This card belongs to a multigene family. The summary below describes the family as a whole and is not specific to this gene; findings specific to PF3D7_0100300, if any, are in the sections that follow.
PfEMP1, encoded by the ~60-member multicopy var gene family, is a hypervariable, high-molecular-weight (200–350 kDa) parasite-derived adhesin exported to the surface of Plasmodium falciparum-infected erythrocytes, where it functions as the principal cytoadherence ligand mediating sequestration and antigenic variation (PMID:6374009, PMID:7606788, PMID:7541722). Its variable extracellular region is built from modular DBL and CIDR domains whose sequence class determines receptor specificity: CIDR1α three-helix bundles bind CD36 (PMID:9786187, PMID:18773118), DBLβ/DBLβmotif domains bind ICAM-1 (PMID:19381252, PMID:23297413, PMID:28279348), CIDRα1 domains bind EPCR to disrupt the brain endothelial barrier in cerebral malaria (PMID:28279348, PMID:29107642), and NTS-DBL1α domains mediate rosetting with uninfected erythrocytes through CR1, heparin/sulfated glycans, and ABO blood-group antigens (PMID:9230440, PMID:20045435, PMID:21402930, PMID:22807674). Domain cassettes DC8/DC13 confer broad binding to brain and other endothelia and are transcriptionally associated with severe pediatric malaria (PMID:22619319, PMID:22619330, PMID:23825944). The distinct variant VAR2CSA is solely responsible for placental sequestration, binding chondroitin sulfate A on syndecan-1 through the cooperative action of its full six-DBL ectodomain—high-affinity, specific binding requires the assembled compact structure rather than isolated domains (PMID:15520249, PMID:16025132, PMID:17562715, PMID:20194779, PMID:33452495), with the DBL2X core forming the minimal binding region (PMID:22570492, PMID:27556547). VAR2CSA CSA binding and surface trafficking are further tuned by phosphorylation, by host/parasite CK2α at S1068 (PMID:39804934) and by the exported kinase FIKK1 at DBL1-3 residues (PMID:42525717). PfEMP1 is exported via a PEXEL/Plasmepsin V- and PTEX-dependent pathway (PMID:24983235, PMID:20170656), trafficked through Maurer's clefts (anchored to the RBC skeleton by SBP1) (PMID:23421990, PMID:25883090), and displayed at knobs where its intracellular ATS/VARC domain is anchored to the erythrocyte cytoskeleton via KAHRP–spectrin interactions and PHIST proteins such as PFE1605w (PMID:10446142, PMID:24983468, PMID:26916885, PMID:28806784); chaperones Hsp70-x/PFA0660w assist this export (PMID:28732045, PMID:30804381), and CLAG9 is required for surface display (PMID:20823248). Only one var gene is expressed at a time, enforced by cis-acting promoter–intron pairing, PfSir2-mediated histone deacetylation and H3K9me3-dependent perinuclear heterochromatin organization, actin-driven repositioning, and intronic antisense lncRNAs, while VAR2CSA is additionally controlled post-transcriptionally by a uORF-mediated translational switch and NMD (PMID:16455655, PMID:17257309, PMID:19402747, PMID:22100161, PMID:25691743, PMID:19119419, PMID:23980802, PMID:28481333, PMID:41851501, PMID:41984626). Beyond adhesion, surface PfEMP1 dampens host innate immunity—suppressing IFN-γ and NF-κB/cytokine responses and evading complement—while its conserved receptor-binding sites are targets of broadly inhibitory antibodies (PMID:18005727, PMID:29038124, PMID:30666256, PMID:39567685, PMID:40833410).
98 family-level findings
| Year | Finding | Species | Conf | PMIDs |
|---|---|---|---|---|
| 1984 | A high-molecular-weight strain-specific antigen (~285,000 Mr for Camp strain, ~260,000 for St. Lucia strain) of parasite origin is exposed on the surface of P. falciparum-infected erythrocytes, accessible to lactoperoxidase-catalyzed radioiodination and trypsin cleavage, and immune sera against it block cytoadherence in a strain-specific fashion. | Plasmodium falciparum | High | 6374009 |
| 1995 | The var gene family encodes 200–350 kDa proteins (PfEMP1) with a variable extracellular segment containing receptor-binding domains, a transmembrane sequence, and a probable submembrane anchor; there are 50–150 var genes distributed across multiple parasite chromosomes, and expression is associated with antigenic and adhesive variation of infected erythrocytes. | Plasmodium falciparum | High | 7606788 |
| 1995 | Cloning of two related PfEMP1 genes from the Malayan Camp (MC) parasite strain confirmed PfEMP1 as the antigenically variant surface protein; antibodies against recombinant protein fragments were MC-strain-specific, reacted with the surface of MC-infected erythrocytes, and blocked adherence to CD36 but not to thrombospondin, identifying CD36 as a binding partner of PfEMP1. | Plasmodium falciparum | High | 7541722 |
| 1995 | Expression of individual var genes correlates with expression of clonally variant surface antigens and with specific cytoadherence phenotypes; expression of a specific var gene correlated with binding to ICAM-1, establishing that individual var gene products determine receptor-binding specificity. | Plasmodium falciparum | High | 7606775 |
| 1997 | PfEMP1, encoded by a specific var gene, is the parasite ligand mediating rosetting (binding of infected erythrocytes to uninfected erythrocytes); complement receptor 1 (CR1) on uninfected erythrocytes is the host receptor for rosetting, and a DBL domain of PfEMP1 binds CR1. | Plasmodium falciparum | High | 9230440 |
| 1998 | A recombinant 179-residue subfragment of PfEMP-1 (rC1-2[1-179]) encompassing the CIDR1 region is the CD36-binding domain; this fragment inhibits and reverses adhesion of parasitized red blood cells to CD36 under physiologically relevant flow conditions in a concentration-dependent, non-strain-specific manner, with no effect on CSA-mediated adhesion. | Plasmodium falciparum | High | 9786187 |
| 1999 | KAHRP directly interacts with the cytoplasmic region of PfEMP1 (VARC); three KAHRP fragments bind VARC, with high-affinity binding (Kd ~10^-7 M) mapped to the histidine-rich and 5' repeat regions of KAHRP; deletion of these regions abolishes binding. This interaction is required for efficient clustering of PfEMP1 at knob structures and for stable cytoadherence under hemodynamic flow. | Plasmodium falciparum | High | 10446142 |
| 2000 | The CIDR domain of PfEMP1 mediates binding to chondroitin sulfate A (CSA) as well as CD36; recombinant CIDR domains from two parasite strains bound CHO cells expressing CSA, and binding was inhibited by chondroitinase ABC treatment and by soluble CSA; a DBL1 domain showed no binding to CHO cells. | Plasmodium falciparum | Medium | 10910712 |
| 2000 | PfEMP1 domain architecture is non-random: DBL and CIDR domains are classified into distinct sequence classes (CIDR: alpha, beta, gamma; DBL: alpha, beta, gamma, delta, epsilon), and certain tandem domain associations (e.g. DBLalpha-CIDRalpha) are preferentially conserved across 20 PfEMP1 sequences, suggesting functional constraints on folding, transport, or binding. | Plasmodium falciparum | Low | 11071284 |
| 2002 | The CIDR1 domain of PfEMP1 (MCvar1) is the minimal CD36-binding domain; a recombinant peptide (PpMC-179) from this domain inhibits cytoadherence of clinical P. falciparum isolates to endothelial cells in vitro and in vivo in a human/SCID mouse chimeric model, and reverses adhesion of already-adherent infected erythrocytes. | Plasmodium falciparum | High | 12393525 |
| 2004 | VAR2CSA is expressed on the surface of CSA-selected infected erythrocytes and is recognized by antibodies from endemic populations in a sex-specific and parity-dependent manner, establishing VAR2CSA as the primary PfEMP1 variant responsible for placental sequestration in pregnancy-associated malaria. | Plasmodium falciparum | High | 15520249 |
| 2004 | Parasites causing severe malaria preferentially transcribe Group A var genes; the Group A gene product PFD1235w/MAL7P1.1 is translated and expressed on the infected erythrocyte surface, linking specific PfEMP1 variants encoded by Group A var genes to the VSA phenotype associated with severe malaria. | Plasmodium falciparum | Medium | 15123742 |
| 2005 | Disruption of the var2csa gene results in loss of the ability of parasites to recover the CSA-binding phenotype, demonstrating that a single var gene member (var2csa) is solely responsible for cytoadhesion to placental chondroitin sulphate A. | Plasmodium falciparum | High | 16025132 |
| 2005 | PfEMP1 is exported across the parasite plasma membrane and parasitophorous vacuole membrane and trafficked through the infected RBC cytoplasm to the erythrocyte surface; a KAHRP N-terminal protein export element appended to PfEMP1 transmembrane and C-terminal domains was sufficient for surface trafficking; FRAP data suggest trafficking as a complex rather than in vesicles. | Plasmodium falciparum | High | 15692070 |
| 2005 | Depletion of cholesterol from the erythrocyte membrane with methyl-beta-cyclodextrin inhibits delivery of PfEMP1 to the erythrocyte surface; the trafficking defect occurs at the level of transfer from Maurer's clefts to the erythrocyte membrane, suggesting PfEMP1 inserts at cholesterol-rich microdomains. | Plasmodium falciparum | Medium | 16682462 |
| 2005 | Haemoglobin C (HbC) causes abnormal surface display of PfEMP1 on infected erythrocytes, resulting in reduced adhesion to CD36 and ICAM-1 and impaired rosetting; the PfEMP1 display abnormalities correlate with markers of erythrocyte senescence and are greater in HbCC than HbAC erythrocytes. | Plasmodium falciparum | High | 15973412 |
| 2005 | Removal of PfEMP1 from infected erythrocyte surfaces, preincubation with anti-PfEMP1 sera, or preincubation with soluble PfEMP1 receptors prior to injection into rats significantly reduced sequestration in vivo; distinct parasite lines with different PfEMP1 binding specificities (CD36, CSA, multiadhesive) showed differential patterns of organ sequestration in the rat model. | Plasmodium falciparum | Medium | 16239578 |
| 2006 | The DBL1alpha domain of PfEMP1 from a rosetting parasite mediates adhesion between infected and uninfected erythrocytes; immunization with a mini-PfEMP1 construct (DBL1alpha-TM-ATS) expressed via Semliki Forest virus generates antibodies that disrupt rosettes and prevent sequestration of P. falciparum-infected erythrocytes in an in vivo model. | Plasmodium falciparum | Medium | 15246600 |
| 2006 | Strict pairing of var promoters and their cognate introns is required for var gene silencing; loss of the intron results in var promoter activation; in multicopy concatamers each intron can silence only one promoter (one-to-one pairing); disruption of silencing of one gene does not affect neighboring var promoters, indicating silencing is regulated at the level of individual genes rather than by broad silent chromatin assembly across chromosomal regions. | Plasmodium falciparum | High | 16455655 |
| 2006 | During gametocyte development, a defined subset of type C var loci is transcribed in a programmed manner regardless of the var expression phenotype of the asexual progenitors, demonstrating that var gene transcriptional regulation in gametocytes is governed by a mechanism distinct from the antigenic variation program in asexual stages. | Plasmodium falciparum | Medium | 16896206 |
| 2006 | Monoclonal antibodies against var2CSA-PfEMP1 block CSA-binding parasite adhesion; the DBL5epsilon and DBL6epsilon domains of var2CSA are identified as the primary targets of cytoadhesion-inhibitory antibodies; purified native var2CSA ligand elicits antibodies that inhibit CSA-binding infected erythrocyte cytoadhesion. | Plasmodium falciparum | Medium | 17095277 |
| 2007 | PfEMP1 (var2csa-encoded) directly binds chondroitin sulfate A (CSA), with binding dependent on 4-O-sulfated disaccharides and glucuronic acid (not iduronic acid), and requires a minimum chain length of eight monosaccharide units. Polymorphisms in var2csa correlate with isolate-specific differences in preferred CSA structural motifs. | Plasmodium falciparum | High | 17562715 |
| 2007 | PfEMP1 suppresses early interferon-gamma production by human peripheral blood mononuclear cells (gammadelta-T, NK, and alphabeta-T cells) in a CD36-independent manner, as demonstrated by comparing wild-type parasites to transgenic parasites lacking PfEMP1 surface expression. | Plasmodium falciparum | High | 18005727 |
| 2007 | Mutually exclusive var gene expression is controlled at the level of RNA polymerase II-mediated transcription initiation during ring stages, not post-transcriptionally. | Plasmodium falciparum | Medium | 17257309 |
| 2007 | var gene silencing and mutually exclusive expression depend on cooperative interactions between the two promoters (upstream and intron) of each var gene, and evidence supports existence of a var-specific subnuclear expression site. | Plasmodium falciparum | Medium | 17762879 |
| 2007 | PfEMP1 interaction with CSA mediates cytoadhesion of P. falciparum-infected erythrocytes to human NK cell lines, but this CSA-mediated adhesion is not required for primary NK cell activation. ICAM-1 engagement with its host ligand LFA-1 (not with PfEMP1 directly) is mandatory for NK cell interferon-gamma response. | Plasmodium falciparum | High | 17311092 |
| 2008 | VAR2CSA harbors IgG- and IgM-binding domains (DBL2-X, DBL5-epsilon, and DBL6-epsilon), and CSA binding and nonimmune IgG/IgM binding are linked phenotypes of adapted parasites. Fresh placental isolates bind IgG/IgM/HA/CSA simultaneously rather than exclusively to CSA. | Plasmodium falciparum | Medium | 16945914 |
| 2008 | The CIDR1alpha domain of PfEMP1 adopts a conserved three-alpha-helix bundle structure (with seven conserved cysteines and 10 conserved hydrophobic residues) that mediates CD36 binding; only CIDR1alpha-class domains bind CD36 despite extensive sequence diversity across PfEMP1 variants. | Plasmodium falciparum | High | 18773118 |
| 2009 | PfSir2A and PfSir2B (NAD+-dependent histone deacetylases) are required for silencing of different var gene subsets classified by conserved promoter type, and in their absence mutually exclusive var gene expression breaks down. Var gene silencing originates within the promoter and PfSir2 paralogues mediate cis spreading of silenced chromatin. PfSir2A (but not PfSir2B) is additionally required for telomeric end protection. | Plasmodium falciparum | High | 19402747 |
| 2009 | The var2csa mRNA contains a small upstream open reading frame (uORF) that represses translation of VAR2CSA protein. This translational repression is reversible, allowing high-level protein production upon selection pressure, providing a mechanism for conditional upregulation in the presence of placental tissue. | Plasmodium falciparum | High | 19119419 |
| 2009 | Ectopic recombination between var genes occurs during mitosis, generating novel var gene variants with disrupted regulation that show persistent activation; the var promoter and intron of the recombined gene are not responsible for altered activity, implicating subtelomeric cis sequences as the cause. | Plasmodium falciparum | Medium | 19389407 |
| 2009 | VAR2CSA DBL6-epsilon domain binds CSPG through a positively charged surface on the distal side of subdomain 2, a structurally distinct binding site from that of DBL3X, which binds CSPG through a positively charged patch and sulfate-binding site on its concave surface. | Plasmodium falciparum | High | 19695262 |
| 2009 | var2csa spontaneously becomes the dominant var gene transcript when parasites are propagated without selective pressure; despite high transcript levels, intracellular VAR2CSA protein levels are low and the protein is not expressed on the erythrocyte surface, indicating post-transcriptional (translational) repression. The gene repositions to the perinuclear area and away from telomeric heterochromatin upon activation. | Plasmodium falciparum | Medium | 18431472 |
| 2009 | DBL2betaC2 domain of PfEMP1 (specifically from Group A PfEMP1 PF11_0521 in 3D7) binds ICAM1 with high affinity; binding is inhibited by immune sera from east Africa but not by US control sera; neutralizing antibodies against this domain are common in immune east African adults but uncommon in children. | Plasmodium falciparum | Medium | 19381252 |
| 2010 | The full-length extracellular region of VAR2CSA (all six DBL domains together) binds CSA with high affinity (Kd = 61 nM) and specificity, whereas individual DBL domains do not recapitulate this specificity. The full-length protein adopts a compact organization governed by interdomain interactions rather than an extended structure. | Plasmodium falciparum | High | 20194779 |
| 2010 | Full-length recombinant VAR2CSA binds chondroitin sulfate proteoglycan with nanomolar affinity and with specificity similar to intact infected erythrocytes, unlike individual DBL domains. Antibodies against full-length VAR2CSA completely inhibit both recombinant VAR2CSA and parasite binding to CSPG. | Plasmodium falciparum | High | 20109466 |
| 2010 | CLAG9 physically interacts with VAR2CSA (a PfEMP1 variant) and is required for surface expression of PfEMP1 on infected erythrocytes. In parasites lacking CLAG9, VAR2CSA fails to traffic to the erythrocyte surface and remains within the parasite. CLAG9 is expressed in two synthesis stages (early ring and late trophozoite) and is located at or near the erythrocyte membrane, with a portion exposed on the cell surface. | Plasmodium falciparum | High | 20823248 |
| 2010 | A single P. falciparum-infected erythrocyte can simultaneously express two different PfEMP1 variants on its surface (demonstrated in a 3D7 sub-line), enabling binding to both CD31/PECAM1 and CD54/ICAM1 and approximately doubling adhesion efficiency to human endothelial cells. | Plasmodium falciparum | Medium | 20824088 |
| 2010 | The NTS-DBL1alpha domain of PfEMP1 (from the VarO rosetting line) mediates rosetting through binding to heparin/sulfated oligosaccharides with micromolar affinity; binding affinity correlates with the degree and position of sulfation. Antibodies against NTS-DBL1alpha disrupt rosettes. | Plasmodium falciparum | High | 20045435 |
| 2010 | Protein export of PfEMP1 begins with entry into the endoplasmic reticulum and concludes with passage across the vacuole membrane via the Plasmodium translocon of exported proteins (PTEX). | Plasmodium falciparum | Low | 20170656 |
| 2011 | PfEMP1-CIDR1alpha binds B cells and increases expression of TLR7 and TLR10 mRNA and sensitizes B cells to TLR9 signaling via MyD88. CIDR1alpha-induced B-cell activation does not proceed through BCR signaling (Lyn/phospho-tyrosine pathways are not activated) but instead induces phosphorylation of ERK1/2, p38, and IKBα. | Plasmodium falciparum | Medium | 21620790 |
| 2011 | In the rosetting parasite clone FCR3S1.2, the dominant PfEMP1 is encoded by FCR3S1.2var2 (IT4var60), not var1; antibodies to the NTS-DBL1alpha of var2 disrupt rosettes (~95%) and recognize the infected erythrocyte surface, identifying this PfEMP1 as the rosetting mediator. | Plasmodium falciparum | Medium | 21266056 |
| 2011 | Perinuclear filamentous actin controls var gene spatial repositioning and mutually exclusive expression: var introns contain an 18 bp nuclear protein-binding element that recruits an actin protein complex; pharmacologically induced F-actin formation repositions intron-carrying episomes and var genes from a repressive to an active perinuclear compartment, disrupting mutually exclusive expression. | Plasmodium falciparum | High | 22100161 |
| 2011 | The NTS-DBL1α1 domain of VarO PfEMP1 mediates rosetting by binding to RBCs; heparin inhibits this interaction in a dose-dependent manner. Crystal structure shows the N-terminal segment (NTS) forms an integral structural part of the DBL1α domain (not a separate component), and mutagenesis/docking locates the heparin-binding site within NTS. | Plasmodium falciparum | High | 21402930 |
| 2011 | CD36 is the most common adhesion partner of PfEMP1, followed by ICAM-1 and TSP-1; UpsA var genes diverged from CD36 binding. CD36 and ICAM-1 binding specificity is highly predictable by adhesion domain sequence classification. UpsA PfEMP1s do not bind CD36 and likely use other sequestration mechanisms. | Plasmodium falciparum | High | 21573138 |
| 2011 | Nonspecific IgM binds to VAR2CSA-expressing infected erythrocytes and masks PfEMP1-specific IgG epitopes (DBL3X and DBL5ε), protecting parasites from FcγR-dependent phagocytosis without compromising VAR2CSA-mediated adhesion to CSA or increasing complement susceptibility. | Plasmodium falciparum | Medium | 21746929 |
| 2011 | The minimal VAR2CSA region retaining high-affinity, specific CSA binding is DBL1X-3X. Inhibitory antibodies raised against full-length DBL1X-6ε principally target DBL3X and, to a lesser extent, DBL5ε. | Plasmodium falciparum | Medium | 21625526 |
| 2012 | Domain cassette 8 (DC8) and DC13 var genes encode PfEMP1 variants associated with severe malaria in children (including cerebral malaria and severe anemia); transcript levels of DC8-encoding var genes are significantly higher in severe versus uncomplicated malaria. | Plasmodium falciparum | Medium | 22619319 |
| 2012 | A specific domain cassette (DC4) present in group A var genes mediates ICAM-1 binding; the ICAM-1 binding capacity maps to the C-terminal third of the DBLβ3 domain of DC4. DC4 is the target of broadly cross-reactive, adhesion-inhibitory IgG antibodies. | Plasmodium falciparum | Medium | 23209327 |
| 2012 | A subset of group A-like var genes (including HB3var3, 3D7_PFD0020c, ITvar7, ITvar19 encoding DC8 or DC13 PfEMP1) are specifically upregulated (11- to >100-fold) after selection on human brain endothelial cells (HBEC-5i). Antibodies to these PfEMP1 variants block binding to HBEC-5i, confirming their adhesive function. | Plasmodium falciparum | High | 22619330 |
| 2012 | The minimal CSA-binding region of VAR2CSA is the DBL2X domain and its flanking interdomain regions; SAXS modeling shows DBL2X is located at the center of the VAR2CSA structure. Mutation of classic sulfate-binding sites indicates CSA binding is not solely dependent on sulfated CSA structure. A small DBL2X-based antigen induces highly adhesion-blocking antibodies. | Plasmodium falciparum | High | 22570492 |
| 2012 | ABO blood group is the main receptor for VarO rosetting, with marked preference for group A > group B > group O. The 2.8 Å crystal structure of the NTS-DBL1α1-CIDR1γ head region reveals extensive DBL1α1-CIDR1γ contacts; direct blood group trisaccharide binding was demonstrated by surface plasmon resonance. The RBC-binding site (opposite to the heparin-binding site) was localized by docking and mutagenesis. | Plasmodium falciparum | High | 22807674 |
| 2012 | The intracellular ATS domain of PfEMP1 shares a unique molecular architecture with a minimal folded core and extensive flexible elements. ATS does not bind KAHRP in solution; instead, ATS associates with PFI1780w (a PHIST family member), representing the first molecular function assigned to any PHIST variant. | Plasmodium falciparum | Medium | 22249178 |
| 2013 | Maurer's cleft cisternae are formed early after invasion; PfEMP1 accumulates near the parasite surface in membranous structures before transfer to pre-formed mobile Maurer's clefts. The tether/Maurer's cleft complex docks onto the RBC membrane at ~20 h post invasion. Electron-dense vesicles may traffic PfEMP1 from Maurer's clefts to the RBC membrane. | Plasmodium falciparum | Medium | 23421990 |
| 2013 | The var2csa upstream open reading frame (uORF) represses translation of the downstream ORF (dORF) encoding VAR2CSA. Relief of this repression requires both active translation of the uORF and sequence-specific characteristics of the surrounding transcript, which together control ribosome reinitiation efficiency, providing a molecular switch for VAR2CSA expression. | Plasmodium falciparum | Medium | 23980802 |
| 2013 | PfEMP1 variant IT4VAR13 binds ICAM-1 exclusively through its DBLβ domain, forming a 1:1 complex. The full ~300 kDa ectodomain is rigid, elongated, and monomeric, with a modular arrangement that exposes the ICAM-1 binding surface. | Plasmodium falciparum | Medium | 23297413 |
| 2013 | DC8 and DC13 var gene-expressing infected erythrocytes bind avidly to diverse endothelial cell types (brain, lung, heart, bone marrow). Multiple extracellular domains of IT4var19 (DC8) bind both brain and non-brain endothelial cells without discriminating between types. Recombinant DC8 and DC13 CIDR1 domains share widespread endothelial binding activity and compete for DC8-IE binding to brain endothelial cells, suggesting a common host receptor. | Plasmodium falciparum | Medium | 23825944 |
| 2013 | DC5-containing PfEMP1 mediates binding to PECAM1; anti-DC5-specific antibodies inhibit binding of DC5-PfEMP1-expressing parasites to human bone marrow endothelial cells. Antibodies against each of the four DC5-characteristic domains react with native PfEMP1 on the IE surface. | Plasmodium falciparum | Medium | 23874884 |
| 2013 | IT/R29 strain expressing IT4var09 (a rosette-mediating PfEMP1) also cytoadheres to brain microvascular endothelial cells (HBEC-5i) via heparan sulfate proteoglycans; this cytoadherence is mediated by the NTS-DBL1α and DBL2γ domains binding heparin (Kd ~0.5 μM), and is distinct from rosetting (which is mediated by NTS-DBL1α binding complement receptor 1). | Plasmodium falciparum | Medium | 24343658 |
| 2014 | PHIST member PFE1605w directly binds the PfEMP1 intracellular ATS segment (Kd = 5 ± 0.6 μM), comigrates with PfEMP1 during export, and localizes to knobs. The crystal structure of a PHIST domain was resolved. A partial NMR-derived model of the PHIST-PfEMP1 interaction was obtained. Control PHIST variants that do not localize to knobs (MAL8P1.4) or bind PfEMP1 30-fold more weakly (PFI1780w) did not show the same comigration pattern. | Plasmodium falciparum | High | 24983468 |
| 2014 | Plasmepsin V (PMV) cleaves the PEXEL motif co-translationally and is essential for protein export including PfEMP1 surface display and cytoadherence; pharmacological inhibition of PMV dose-dependently impairs PEXEL processing, PfEMP1 display on the erythrocyte surface, and cytoadherence, killing parasites at the trophozoite stage. | Plasmodium falciparum, Plasmodium vivax | High | 24983235 |
| 2015 | Antisense long noncoding RNAs (lncRNAs) from var introns are associated with the single active var gene during the cell cycle window when the upstream promoter is active. These lncRNAs are incorporated into chromatin, and their expression in trans triggers activation of a silent var gene in a sequence- and dose-dependent manner. Interference with these lncRNAs using PNA molecules downregulates the active var gene and induces expression switching. | Plasmodium falciparum | Medium | 25691743 |
| 2015 | α2-Macroglobulin (α2M) is both required and sufficient for rosetting mediated by HB3VAR06 PfEMP1; the α2M binding site maps to the C-terminal end of HB3VAR06. α2M can crosslink at least four HB3VAR06 molecules, augmenting avidity for host receptors. IgM works synergistically with α2M to lower the concentration required for rosetting, but IgM alone cannot induce rosetting. | Plasmodium falciparum | Medium | 26134405 |
| 2015 | Knob density on the infected erythrocyte surface is linked to the specific PfEMP1 variant expressed: selection for IT4VAR32b expression increased knob density ~3-fold, while IT4VAR60-expressing IEs were essentially knobless. KAHRP was expressed in all sublines regardless of PfEMP1 variant, indicating PfEMP1 identity—not KAHRP expression—determines knob density. | Plasmodium falciparum | Medium | 26443460 |
| 2015 | Skeleton-binding protein 1 (SBP1) binds specifically to defined sub-domains of RBC membrane skeleton proteins 4.1R and spectrin, anchoring Maurer's clefts to the RBC membrane skeleton. These interactions are necessary but not sufficient for PfEMP1 translocation to the RBC surface; the N-terminal domain of SBP1 within the MC lumen plays an additional essential but undefined role. | Plasmodium falciparum | Medium | 25883090 |
| 2015 | var gene architecture (modular domain structure, mosaicism) is conserved across the Laverania subgenus including ape Plasmodium species (e.g., P. gaboni), indicating the modular genetic architecture underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, predating the emergence of P. falciparum. | Plasmodium falciparum, Plasmodium gaboni | Low | 26456841 |
| 2016 | The PHIST protein PFE1605w directly interacts with both the intracellular segment of PfEMP1 and with erythrocyte cytoskeletal components; conditional reduction of PFE1605w strongly reduces adhesion of infected erythrocytes to CD36 but does not affect PfEMP1 transport, establishing PHIST proteins as anchors linking PfEMP1 to the host cytoskeleton at knobs. | Plasmodium falciparum | High | 26916885 |
| 2016 | DC8-type PfEMP1 mediates binding of infected erythrocytes to gC1qR through conserved surface epitopes in the DBLβ12 domain; polyclonal antibodies against DBLβ12 inhibit gC1qR binding of multiple P. falciparum isolates by ~50%. | Plasmodium falciparum | Medium | 27835682 |
| 2017 | Structural biology of PfEMP1 DBLβ domains revealed a sequence motif that predicts ICAM-1 binding; ICAM-1-binding PfEMP1s also interact with EPCR, allowing dual-receptor binding via the same molecule; expression of these dual-binding (ICAM-1 + EPCR) PfEMP1s is associated with increased risk of cerebral malaria. | Plasmodium falciparum | High | 28279348 |
| 2017 | A recombinant CIDRα1.7 domain of PfEMP1 (from a pediatric cerebral malaria brain autopsy isolate) inhibits the barrier-protective properties of EPCR in human brain endothelial cells in vitro, providing a direct mechanistic link between EPCR-binding CIDRα1 PfEMP1 domains and brain endothelial barrier disruption. | Plasmodium falciparum | Medium | 29107642 |
| 2017 | The PfEMP1 cytosolic domain interacts broadly with erythrocyte α-spectrin (with weak preference for domain 17), while KAHRP preferentially associates with β-spectrin domains 10–14; these interactions support knob formation and cytoadherence. | Plasmodium falciparum | Medium | 28806784 |
| 2017 | The P. falciparum translation-enhancing factor (PTEF) relieves upstream open reading frame (uORF) repression of var2csa mRNA to facilitate VAR2CSA protein production; PTEF requires proteolytic cleavage by PfCalpain, generating a C-terminal domain with a sterile-alpha-motif-like region that shuttles to the cytoplasm and interacts with ribosomes to derepress translation of VAR2CSA. | Plasmodium falciparum | High | 28481333 |
| 2017 | PfEMP1 expressed on the infected erythrocyte surface dampens NF-κB activation and reduces TNF, IL-10, IL-1β, IL-6, MCP-1, MIP-1α, and MIP-1β release from macrophages/monocytes; VAR2CSA-type PfEMP1-containing parasites induced particularly reduced cytokine responses compared to PfEMP1-null parasites. | Plasmodium falciparum | Medium | 29038124 |
| 2017 | Human miR-451 and miR-140 delivered via RBC-derived microparticles containing hAgo2 bind to A and B subgroup var gene transcripts and downregulate PfEMP1 expression in P. falciparum, representing a host innate resistance mechanism. | Plasmodium falciparum | Low | 28831191 |
| 2017 | Knockout of the exported chaperone Hsp70-x delays PfEMP1 export to the infected erythrocyte surface and reduces IE adhesion, indicating that Hsp70-x facilitates efficient export and surface presentation of PfEMP1. | Plasmodium falciparum | Medium | 28732045 |
| 2018 | P. falciparum Kelch13 (K13) colocalizes and co-purifies with PfEMP1 at PI3P tubules/vesicles of the parasite ER; K13 mutants show altered PfEMP1 export to the red cell and reduced cytoadherence to a host endothelial receptor, implicating PI3P vesicle amplification in PfEMP1 export. | Plasmodium falciparum | Medium | 29363540 |
| 2018 | A specific PfEMP1 variant (NF54_SpzPfEMP1, encoded by a euchromatic var gene) is expressed on the surface of P. falciparum sporozoites; antibodies against NF54_SpzPfEMP1 block hepatocyte infection in a strain-specific manner, and human volunteers immunized with infective sporozoites developed antibodies against this PfEMP1. | Plasmodium falciparum | Medium | 29539423 |
| 2018 | VAR2CSA mediates placental sequestration specifically through chondroitin sulfate (CS) chains on syndecan-1 expressed on placental syncytiotrophoblasts; VAR2CSA binding to placental CS impairs syndecan-1-related Src signaling in syncytially fused cells. | Plasmodium falciparum | Medium | 27556547 |
| 2018 | IEs expressing DC13 PfEMP1 variants (HB3var03 or IT4var07) do not bind EPCR on plastic, and binding of these DC13 variants to brain endothelial cells is not dependent on EPCR; DC8 variant IT4var19 IEs do bind EPCR, but this interaction is inhibited by normal human serum/plasma, revealing a discrepancy between recombinant protein binding and native IE binding. | Plasmodium falciparum | Medium | 29339517 |
| 2018 | PfEMP1 is detected in extracellular vesicles (EVs) from early-stage (up to 12 hr post-invasion) P. falciparum-infected RBCs; EV origin is from inside the iRBC (not the surface), established using PfEMP1 transport knockout parasites; EVs from PfEMP1-knockout parasites induce more transcriptomic changes in monocytes, suggesting PfEMP1 within EVs modulates host immune responses. | Plasmodium falciparum | Medium | 29349926 |
| 2019 | The exported P. falciparum co-chaperone PFA0660w (Hsp40) binds cholesterol and forms a complex with PfHsp70-x, which in turn directly interacts with the cytoplasmic tail of PfEMP1 in vitro, supporting the model that the PFA0660w–PfHsp70-x pair assists PfEMP1 transport through cholesterol-containing J-dots. | Plasmodium falciparum | Low | 30804381 |
| 2019 | VAR2CSA (rVAR2) binds a distinct type of chondroitin sulfate (CS) modification present on cancer cells, linked to CD44 and CSPG4; rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin inhibits tumor cell growth and metastasis in vivo, establishing the VAR2CSA CS-binding mechanism as targetable in cancer. | Plasmodium falciparum | Medium | 26461094 |
| 2019 | PfEMP1 displayed on infected erythrocytes prevents activation of the classical complement pathway; even when opsonized by PfEMP1-specific IgG, IEs do not activate complement detectable by flow cytometry; engineering a VAR2CSA-specific monoclonal antibody to allow hexamerization enables complement activation only in optimized ELISA conditions but not on native IEs, revealing a parasite strategy of PfEMP1 surface display to evade complement. | Plasmodium falciparum | Medium | 30666256 |
| 2019 | In 3D engineered human brain microvessels under physiological flow, DC8-PfEMP1-expressing IEs decrease binding upon TNF-α activation of endothelium (due to decreased EPCR surface expression), while group B PfEMP1-expressing IEs increase binding (due to increased ICAM-1), demonstrating that EPCR and ICAM-1 mediate the differential adhesion phenotypes of PfEMP1 variants in brain microvessels. | Plasmodium falciparum | Medium | 31138740 |
| 2021 | Cryo-EM structures of full-length VAR2CSA ectodomain (NF54 in complex with CSA, and FCR3 alone) reveal an architecture with a stable core flanked by a flexible arm; CSA binds within two channels in the core without inducing major conformational changes; CSA-binding elements are conserved across VAR2CSA variants while flanking polymorphic segments show evidence of immune selection. | Plasmodium falciparum | High | 33452495 |
| 2021 | Naturally acquired PfEMP1-specific IgG is strongly afucosylated in an exposure-dependent manner and efficiently induces FcγRIIIa-dependent NK cell degranulation; in contrast, immunization with a VAR2CSA subunit vaccine induces fully fucosylated IgG, which has substantially lower FcγRIIIa affinity. | Plasmodium falciparum | Medium | 34611164 |
| 2022 | Neutrophils recognize and kill P. falciparum-infected red blood cells through an interaction between neutrophil ICAM-1 and specific PfEMP1 variants implicated in cerebral malaria, establishing a mechanism of innate immune killing of iRBCs. | Plasmodium falciparum | Medium | 35417070 |
| 2024 | Two broadly reactive human monoclonal antibodies inhibit PfEMP1-EPCR binding by targeting three highly conserved amino acid residues in the EPCR-binding site of CIDRα1 domains; structural analysis of antibody-CIDRα1 complexes revealed a shared binding mechanism across five of six CIDRα1 subclasses, and both antibodies inhibited parasite sequestration in 3D human brain microvessels under flow. | Plasmodium falciparum | High | 39567685 |
| 2024 | PfEMP1 variant PF3D7_0412900 (expressed by 3D7A) mediates robust rosetting through its CIDRγ2 domain interacting with glycophorin B on uninfected RBC surfaces; antibodies against CIDRγ2 reduced rosetting, identifying glycophorin B as a novel rosetting receptor. | Plasmodium falciparum | Medium | 38309398 |
| 2025 | Human and P. falciparum Casein Kinase 2α (CK2α) phosphorylate the extracellular region of VAR2CSA at residue S1068; this phosphorylation is required for VAR2CSA trafficking to the iRBC surface and for iRBC adhesion to chondroitin sulfate A (CSA). CRISPR/Cas9 mutation of S1068 to alanine abolishes VAR2CSA surface translocation and strongly impairs CSA binding. | Plasmodium falciparum | High | 39804934 |
| 2025 | Selection-linked integration (SLI) can force all parasites in a population to express the same PfEMP1 variant, enabling genetic modification of the expressed var locus. Using SLI in IT4 strain, parasites with effective receptor-binding capacity were generated, enabling studies of PfEMP1 trafficking, identification of the protein environment of functional PfEMP1, and discovery of new proteins required for PfEMP1-mediated sequestration. | Plasmodium falciparum | Medium | 41460168 |
| 2025 | DC15 (DBLα1.2-CIDRα1.5b) and DC8-like PfEMP1 variants mediate rosetting in addition to the previously known DC11 and DC16 types, expanding the set of PfEMP1 structural types capable of rosetting; rosette-mediating PfEMP1 were identified by var gene transcription profiling, surface expression assays, rosette disruption, and erythrocyte binding functional assays. | Plasmodium falciparum | Medium | 39804943 |
| 2025 | A mouse monoclonal antibody (mAb02) targeting DBLβmotif domains of PfEMP1 (associated with dual EPCR and ICAM-1 binding) inhibits PfEMP1 binding to ICAM-1 and iRBC adhesion to ICAM-1. The mAb02 epitope maps to an unfolded linker region of the ICAM-1-binding site of DBLβmotif, including residues directly involved in DBLβmotif-ICAM-1 interaction. | Plasmodium falciparum | Medium | 41053123 |
| 2025 | Broadly reactive and EPCR-binding-inhibitory human monoclonal antibodies against CIDRα1 isolated from a 9-year-old child share an epitope overlapping the EPCR-binding site; structural analysis shows these antibodies contact a few conserved CIDRα1 residues (shared with previously identified mAbs C7 and C74), and additional variable residues reduce their breadth relative to C7/C74. | Plasmodium falciparum | High | 40833410 |
| 2026 | Transient activation of the var2csa locus mediates var gene switching; non-coding RNAs expressed from the var2csa locus contribute to repression of var2csa transcription and affect var switching frequencies. An upstream open reading frame (uORF) in the 5'-UTR of the var2csa transcript destabilizes var2csa mRNA through nonsense-mediated RNA decay (NMD), which in turn promotes transcriptional activation of an alternative var gene. | Plasmodium falciparum | Medium | 41851501 |
| 2026 | Febrile temperature increases transcript levels of exported parasite genes involved in PfEMP1 trafficking and accelerates PfEMP1 surface display in ring-stage infected erythrocytes, leading to a 2-fold increase in ring-stage IE binding in a perfusable 3D human brain microvessel model. | Plasmodium falciparum | Medium | 40929367 |
| 2026 | var2csa transcriptional activation is associated with depletion of repressive H3K9me3 chromatin marks and a small but significant repositioning of the var2csa locus away from heterochromatic telomeric clusters, as determined by chromatin conformation capture. 5-methylcytosine occupancy is present in all var genes but is independent of transcriptional repression and switching. | Plasmodium falciparum | Medium | 41984626 |
| 2026 | FIKK1 kinase phosphorylates VAR2CSA in vitro on multiple residues including S429 and T934 of DBL1-3 domains; this phosphorylation increases binding of recombinant VAR2CSA to CSA. FIKK1 co-localizes with VAR2CSA at Maurer's Clefts. Rapamycin-induced knockout of FIKK1 reduces iRBC cytoadhesion to CSA without affecting VAR2CSA protein levels, establishing FIKK1 as a regulator of VAR2CSA-mediated sequestration. | Plasmodium falciparum | High | 42525717 |
Mechanistic narrative
Synthesis pass · prose summary of the discoveries below
No mechanistic discoveries found in literature.
Mechanism profile
Synthesis pass · controlled-vocabulary classification
No controlled-vocabulary terms were assigned to this entry.
Source papers
Stage 0 corpus · 100 papers · ranked by NIH iCite citations
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2008 | Antigenic variation in Plasmodium falciparum. | Annual review of microbiology | 338 | 18785843 |
| 2010 | Plasmodium falciparum erythrocyte membrane protein 1 diversity in seven genomes--divide and conquer. | PLoS computational biology | 295 | 20862303 |
| 2000 | Classification of adhesive domains in the Plasmodium falciparum erythrocyte membrane protein 1 family. | Molecular and biochemical parasitology | 224 | 11071284 |
| 2012 | Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children. | Proceedings of the National Academy of Sciences of the United States of America | 222 | 22619319 |
| 2006 | A family affair: var genes, PfEMP1 binding, and malaria disease. | Current opinion in microbiology | 221 | 16814594 |
| 2009 | Sir2 paralogues cooperate to regulate virulence genes and antigenic variation in Plasmodium falciparum. | PLoS biology | 199 | 19402747 |
| 2013 | Malaria's deadly grip: cytoadhesion of Plasmodium falciparum-infected erythrocytes. | Cellular microbiology | 179 | 23957661 |
| 2017 | Variant surface antigens of Plasmodium falciparum and their roles in severe malaria. | Nature reviews. Microbiology | 171 | 28603279 |
| 2003 | Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind. | Microbes and infection | 157 | 12919858 |
| 2017 | Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria. | Cell host & microbe | 154 | 28279348 |
| 2015 | PfEMP1 - A Parasite Protein Family of Key Importance in Plasmodium falciparum Malaria Immunity and Pathogenesis. | Advances in parasitology | 137 | 25911365 |
| 2000 | Molecular aspects of severe malaria. | Clinical microbiology reviews | 125 | 10885986 |
| 2014 | Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates. | Cellular and molecular life sciences : CMLS | 120 | 24691798 |
| 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 |
| 2019 | Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it. | Immunological reviews | 109 | 31562653 |
| 2008 | PfEMP1: an antigen that plays a key role in the pathogenicity and immune evasion of the malaria parasite Plasmodium falciparum. | The international journal of biochemistry & cell biology | 107 | 19150410 |
| 2012 | A novel domain cassette identifies Plasmodium falciparum PfEMP1 proteins binding ICAM-1 and is a target of cross-reactive, adhesion-inhibitory antibodies. | Journal of immunology (Baltimore, Md. : 1950) | 103 | 23209327 |
| 2017 | Linking EPCR-Binding PfEMP1 to Brain Swelling in Pediatric Cerebral Malaria. | Cell host & microbe | 95 | 29107642 |
| 2010 | Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. | PLoS pathogens | 89 | 20824088 |
| 2001 | Decoding the language of var genes and Plasmodium falciparum sequestration. | Trends in parasitology | 84 | 11872399 |
| 2004 | var genes, PfEMP1 and the human host. | Molecular and biochemical parasitology | 83 | 14747137 |
| 2018 | Remodeling of the malaria parasite and host human red cell by vesicle amplification that induces artemisinin resistance. | Blood | 82 | 29363540 |
| 2007 | PfEMP1-DBL1alpha amino acid motifs in severe disease states of Plasmodium falciparum malaria. | Proceedings of the National Academy of Sciences of the United States of America | 78 | 17895392 |
| 2016 | Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains. | EMBO molecular medicine | 77 | 27354391 |
| 2017 | Parasites Causing Cerebral Falciparum Malaria Bind Multiple Endothelial Receptors and Express EPCR and ICAM-1-Binding PfEMP1. | The Journal of infectious diseases | 71 | 28863469 |
| 2014 | A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface. | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 69 | 24983468 |
| 2014 | The role of PfEMP1 adhesion domain classification in Plasmodium falciparum pathogenesis research. | Molecular and biochemical parasitology | 68 | 25064606 |
| 2009 | The role of platelets in the pathogenesis of cerebral malaria. | Cellular and molecular life sciences : CMLS | 67 | 20091081 |
| 2018 | Extracellular vesicles from early stage Plasmodium falciparum-infected red blood cells contain PfEMP1 and induce transcriptional changes in human monocytes. | Cellular microbiology | 65 | 29349926 |
| 2017 | The Severity of Plasmodium falciparum Infection Is Associated with Transcript Levels of var Genes Encoding Endothelial Protein C Receptor-Binding P. falciparum Erythrocyte Membrane Protein 1. | Infection and immunity | 64 | 28138022 |
| 2017 | Red blood cells release microparticles containing human argonaute 2 and miRNAs to target genes of Plasmodium falciparum. | Emerging microbes & infections | 64 | 28831191 |
| 2013 | Spatial and temporal mapping of the PfEMP1 export pathway in Plasmodium falciparum. | Cellular microbiology | 62 | 23421990 |
| 2009 | High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies. | PLoS pathogens | 61 | 19381252 |
| 2013 | How malaria modulates memory: activation and dysregulation of B cells in Plasmodium infection. | Trends in parasitology | 59 | 23562778 |
| 2007 | Haemoglobin C and S role in acquired immunity against Plasmodium falciparum malaria. | PloS one | 59 | 17912355 |
| 2012 | Abnormal PfEMP1/knob display on Plasmodium falciparum-infected erythrocytes containing hemoglobin variants: fresh insights into malaria pathogenesis and protection. | Microbes and infection | 56 | 22634344 |
| 2021 | Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination. | Nature communications | 54 | 34611164 |
| 2010 | The role of Plasmodium falciparum variant surface antigens in protective immunity and vaccine development. | Human vaccines | 53 | 19823032 |
| 2008 | Default Pathway of var2csa switching and translational repression in Plasmodium falciparum. | PloS one | 53 | 18431472 |
| 2001 | Parasite adhesion and immune evasion in placental malaria. | Trends in parasitology | 52 | 11423376 |
| 2003 | Plasmodium falciparum adhesion in the placenta. | Current opinion in microbiology | 51 | 12941407 |
| 2015 | α2-Macroglobulin Can Crosslink Multiple Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) Molecules and May Facilitate Adhesion of Parasitized Erythrocytes. | PLoS pathogens | 50 | 26134405 |
| 2019 | Binding Heterogeneity of Plasmodium falciparum to Engineered 3D Brain Microvessels Is Mediated by EPCR and ICAM-1. | mBio | 49 | 31138740 |
| 2017 | The exported chaperone Hsp70-x supports virulence functions for Plasmodium falciparum blood stage parasites. | PloS one | 49 | 28732045 |
| 2017 | Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria. | BMC medicine | 48 | 29025399 |
| 2012 | α-Thalassemia impairs the cytoadherence of Plasmodium falciparum-infected erythrocytes. | PloS one | 48 | 22623996 |
| 2004 | Immunization with PfEMP1-DBL1alpha generates antibodies that disrupt rosettes and protect against the sequestration of Plasmodium falciparum-infected erythrocytes. | Vaccine | 48 | 15246600 |
| 2006 | Characterization of anti-var2CSA-PfEMP1 cytoadhesion inhibitory mouse monoclonal antibodies. | Microbes and infection | 46 | 17095277 |
| 2016 | The role of PfEMP1 as targets of naturally acquired immunity to childhood malaria: prospects for a vaccine. | Parasitology | 45 | 26741401 |
| 2007 | Dissection of the role of PfEMP1 and ICAM-1 in the sensing of Plasmodium-falciparum-infected erythrocytes by natural killer cells. | PloS one | 45 | 17311092 |
| 2011 | Immunisation with recombinant PfEMP1 domains elicits functional rosette-inhibiting and phagocytosis-inducing antibodies to Plasmodium falciparum. | PloS one | 43 | 21305024 |
| 2004 | The microcirculation in severe malaria. | Microcirculation (New York, N.Y. : 1994) | 43 | 15513866 |
| 2011 | var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2. | Malaria journal | 40 | 21266056 |
| 2011 | TLRs innate immunereceptors and Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) CIDR1α-driven human polyclonal B-cell activation. | Acta tropica | 40 | 21620790 |
| 2017 | Three Is a Crowd - New Insights into Rosetting in Plasmodium falciparum. | Trends in parasitology | 38 | 28109696 |
| 2000 | Malaria multigene families: the price of chronicity. | Parasitology today (Personal ed.) | 38 | 10637585 |
| 2019 | Cholesterol bound Plasmodium falciparum co-chaperone 'PFA0660w' complexes with major virulence factor 'PfEMP1' via chaperone 'PfHsp70-x'. | Scientific reports | 37 | 30804381 |
| 2001 | Molecular mechanisms of Plasmodium falciparum placental adhesion. | Cellular microbiology | 37 | 11260135 |
| 2011 | Antibodies against PfEMP1, RIFIN, MSP3 and GLURP are acquired during controlled Plasmodium falciparum malaria infections in naïve volunteers. | PloS one | 35 | 22174947 |
| 2013 | Plasmodium falciparum expressing domain cassette 5 type PfEMP1 (DC5-PfEMP1) bind PECAM1. | PloS one | 34 | 23874884 |
| 2002 | Human complement receptor type 1 (CR1) binds to a major malarial adhesin. | Trends in molecular medicine | 34 | 12421687 |
| 2010 | Of mice and women: rodent models of placental malaria. | Trends in parasitology | 33 | 20605743 |
| 2002 | Recombinant PfEMP1 peptide inhibits and reverses cytoadherence of clinical Plasmodium falciparum isolates in vivo. | Blood | 32 | 12393525 |
| 2019 | Evasion of Classical Complement Pathway Activation on Plasmodium falciparum-Infected Erythrocytes Opsonized by PfEMP1-Specific IgG. | Frontiers in immunology | 30 | 30666256 |
| 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 |
| 2010 | Protein export in Plasmodium parasites: from the endoplasmic reticulum to the vacuolar export machine. | International journal for parasitology | 30 | 20170656 |
| 2005 | Clinical and molecular aspects of severe malaria. | Anais da Academia Brasileira de Ciencias | 30 | 16127552 |
| 2018 | Natural and Vaccine-Induced Acquisition of Cross-Reactive IgG-Inhibiting ICAM-1-Specific Binding of a Plasmodium falciparum PfEMP1 Subtype Associated Specifically with Cerebral Malaria. | Infection and immunity | 29 | 29426042 |
| 2017 | Regulation of PfEMP1-VAR2CSA translation by a Plasmodium translation-enhancing factor. | Nature microbiology | 29 | 28481333 |
| 2007 | Structural basis for binding of Plasmodium falciparum erythrocyte membrane protein 1 to chondroitin sulfate and placental tissue and the influence of protein polymorphisms on binding specificity. | The Journal of biological chemistry | 29 | 17562715 |
| 2021 | Common virulence gene expression in adult first-time infected malaria patients and severe cases. | eLife | 28 | 33908865 |
| 2017 | Plasmodium falciparum PfEMP1 Modulates Monocyte/Macrophage Transcription Factor Activation and Cytokine and Chemokine Responses. | Infection and immunity | 28 | 29038124 |
| 2016 | Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton. | Cellular microbiology | 27 | 26916885 |
| 2015 | Interactions between Plasmodium falciparum skeleton-binding protein 1 and the membrane skeleton of malaria-infected red blood cells. | Biochimica et biophysica acta | 26 | 25883090 |
| 2015 | Plasmodium falciparum-infected erythrocyte knob density is linked to the PfEMP1 variant expressed. | mBio | 25 | 26443460 |
| 2010 | Biochemical and biophysical characterisation of DBL1alpha1-varO, the rosetting domain of PfEMP1 from the VarO line of Plasmodium falciparum. | Molecular and biochemical parasitology | 25 | 20045435 |
| 2022 | Neutrophils impose strong immune pressure against PfEMP1 variants implicated in cerebral malaria. | EMBO reports | 24 | 35417070 |
| 2018 | Infected erythrocytes expressing DC13 PfEMP1 differ from recombinant proteins in EPCR-binding function. | Proceedings of the National Academy of Sciences of the United States of America | 24 | 29339517 |
| 2005 | Whole-body imaging of sequestration of Plasmodium falciparum in the rat. | Infection and immunity | 24 | 16239578 |
| 2000 | Plasmodium falciparum: cloned and expressed CIDR domains of PfEMP1 bind to chondroitin sulfate A. | Experimental parasitology | 24 | 10910712 |
| 2024 | Broadly inhibitory antibodies to severe malaria virulence proteins. | Nature | 21 | 39567685 |
| 2024 | PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity. | Advances in parasitology | 14 | 39095112 |
| 2025 | Variable surface antigen expression, virulence, and persistent infection by Plasmodium falciparum malaria parasites. | Microbiology and molecular biology reviews : MMBR | 9 | 39807932 |
| 2024 | Antibodies to PfEMP1 and variant surface antigens: Protection after controlled human malaria infection in semi-immune Kenyan adults. | The Journal of infection | 8 | 39182654 |
| 2025 | Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria. | Nature communications | 6 | 39747065 |
| 2025 | Fc-Afucosylation of VAR2CSA-Specific Immunoglobulin G and Clinical Immunity to Placental Plasmodium falciparum Malaria. | The Journal of infectious diseases | 5 | 39585195 |
| 2025 | Plasmodium falciparum expresses fewer var genes at lower levels during asymptomatic dry season infections than clinical malaria cases. | PLoS pathogens | 5 | 40493675 |
| 2025 | Identification of broadly inhibitory anti-PfEMP1 antibodies by mass spectrometry sequencing of plasma IgG from a malaria-exposed child. | Proceedings of the National Academy of Sciences of the United States of America | 5 | 40833410 |
| 2025 | A paradoxical population structure of var DBLα types in Africa. | PLoS pathogens | 4 | 39903780 |
| 2025 | Immune evasion runs in the family: two surface protein families of Plasmodium falciparum-infected erythrocytes. | Current opinion in microbiology | 4 | 40112571 |
| 2025 | A system for functional studies of the major virulence factor of malaria parasites. | eLife | 3 | 41460168 |
| 2025 | Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype. | PLoS pathogens | 2 | 39804943 |
| 2025 | Var genes, strain hyperdiversity, and malaria transmission dynamics. | Trends in parasitology | 2 | 40393890 |
| 2025 | The role of periostin (OSF-2) in the cytoadherence phenomena mediated by malaria parasites. | Frontiers in cellular and infection microbiology | 2 | 40433670 |
| 2025 | Breaking the bind: PfEMP1-specific antibodies in cerebral malaria. | Frontiers in immunology | 2 | 41246335 |
| 2026 | Antibody levels to variant and conserved Plasmodium falciparum antigens predict reduction in parasite burden in Malian children. | Frontiers in immunology | 1 | 41607793 |
| 2025 | A monoclonal antibody selectively recognizing PfEMP1 proteins associated with cerebral malaria. | Scientific reports | 1 | 41053123 |
| 2026 | Febrile Temperature Augments Ring-stage Plasmodium falciparum Adhesion to Brain Endothelial Cells. | The Journal of infectious diseases | 0 | 40929367 |
| 2026 | Mechanistic insights into coordinated var transcriptional switching in malaria parasites. | The EMBO journal | 0 | 41851501 |
| 2026 | Predictive value of PfEMP1 antibody profiles for the course of controlled human malaria infections. | PLoS pathogens | 0 | 42341059 |