ArticlePloS one2015
Binding of subdomains 1/2 of PfEMP1-DBL1α to heparan sulfate or heparin mediates Plasmodium falciparum rosetting.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria.PloS one · 2017Trial
- Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype.PLoS pathogens · 2025Article
- Article
- Variable Surface Antigens ofProtein and peptide letters · 2024Review
- SEVUparin as a potential Adjunctive Treatment in children with severe malaria: A phase I trial safety and dose finding trial (SEVUSMAART).Wellcome open research · 2023Article
- Expression of Single-Domain Soluble and Disulfide-Folded PfEMP1 Antigens in the Escherichia coli SHuffle Expression System.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Repurposing Heparin as Antimalarial: Evaluation of Multiple Modifications Toward In Vivo Application.Pharmaceutics · 2020Article
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
- Rosetting revisited: a critical look at the evidence for host erythrocyte receptors inParasitology · 2020Review
- Sticking for a Cause: The Falciparum Malaria Parasites Cytoadherence Paradigm.Frontiers in immunology · 2019Review
- A new heparan sulfate from the mollusk Nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of Plasmodium falciparum.Memorias do Instituto Oswaldo Cruz · 2019Article
- Leishmaniasis and glycosaminoglycans: a future therapeutic strategy?Parasites & vectors · 2018Review
- Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria.BMC medicine · 2017Article
- Variant surface antigens of Plasmodium falciparum and their roles in severe malaria.Nature reviews. Microbiology · 2017Review
- Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains.EMBO molecular medicine · 2016Article
- Functional analysis of monoclonal antibodies against the Plasmodium falciparum PfEMP1-VarO adhesin.Malaria journal · 2016Article
- Evasion of Immunity to Plasmodium falciparum: Rosettes of Blood Group A Impair Recognition of PfEMP1.PloS one · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The capacity of Plasmodium falciparum parasitized erythrocytes (pRBC) to adhere to the endothelial lining in the microvasculature and to red blood cells (RBC) is associated with the virulence of the parasite, the pathogenesis and development of severe malaria. Rosetting, the binding of uninfected RBC to pRBC, is frequently observed in individuals with severe malaria and is mediated by the N-terminal NTS-DBL1α domain of the adhesin Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) expressed at the surface of the pRBC. Heparan sulfate has been suggested to be an important receptor for the NTS-DBL1α variant IT4(var60) expressed by the parasite FCR3S1.2. Here, we have determined the binding site of NTS-DBL1α (IT4(var60)) to the RBC and heparin using a set of recombinant, mutated proteins expressed in and purified from E. coli. All the variants were studied for their ability to bind to RBC, their capacities to disrupt FCR3S1.2 rosettes, their affinities for heparin and their binding to rosette-disruptive mAbs. Our results suggest that NTS-DBL1α mediates binding to RBC through a limited number of basic amino acid residues localized on the surface of subdomains 1 (SD1) and 2 (SD2). The SD2-binding site is localized in close proximity to one of two previously identified binding sites in the rosetting PfEMP1 of the parasite PaloAlto-varO. The binding site in SD2 of NTS-DBL1α could represent a template for the development of anti-rosetting drugs.
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