ArticleCell host & microbe2015
Structural conservation despite huge sequence diversity allows EPCR binding by the PfEMP1 family implicated in severe childhood malaria.
Article in Cell host & microbe, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses that pooled it.
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Who cites it
123 citing papers in PubMed, 2 syntheses or guidelines pooled it, 194 citations in OpenAlex.
- Meta-Analysis of Human Antibodies AgainstFrontiers in immunology · 2022Pooled it
- Meta-analysis of Plasmodium falciparummBio · 2019Pooled it
- Longitudinal analysis of naturally acquired PfEMP1 CIDR domain variant antibodies identifies associations with malaria protection.JCI insight · 2020Trial
- Article
- Longitudinal plasma metabolomics reveals a role for taurine in asymptomatic malaria and seasonal persistence.Nature microbiology · 2026Article
- A subset of Plasmodium falciparum RIFINs is linked to severe malaria risk reduction and engages LILRB1 through a conserved structural motif.EBioMedicine · 2025Article
- A monoclonal antibody selectively recognizing PfEMP1 proteins associated with cerebral malaria.Scientific reports · 2025Article
- 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 · 2025Article
- Article
- Diamonds in the rif: Alignment-free comparative genomics analysis reveals strain-transcendent Plasmodium falciparum antigens amidst extensive genetic diversity.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2025Article
- Breaking the bind: PfEMP1-specific antibodies in cerebral malaria.Frontiers in immunology · 2025Review
- Antimalarial and neuroprotective effects of ethanolic extracts of the five-flower remedy in an experimental cerebral malaria model.PloS one · 2025Article
- Unveiling new perspectives about the onset of neurological and cognitive deficits in cerebral malaria: exploring cellular and neurochemical mechanisms.Frontiers in cellular and infection microbiology · 2025Review
- Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype.PLoS pathogens · 2025Article
- Plasma From Older Children in Malawi Inhibits Plasmodium falciparum Binding in 3-Dimensional Brain Microvessels.The Journal of infectious diseases · 2024Article
- Article
- Human antibodies offer broad inhibition against variable proteins of the malaria parasite.Nature · 2024Article
- Antibodies to PfEMP1 and variant surface antigens: Protection after controlled human malaria infection in semi-immune Kenyan adults.The Journal of infection · 2024Article
- Differences in phenotype between long-lived memory B cells against Plasmodium falciparum merozoite antigens and variant surface antigens.PLoS pathogens · 2024Article
- Children with hemoglobin C or S trait have low serologic responses to a subset of malaria variant surface antigens.The Journal of infection · 2024Article
63 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRα1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRα1:EPCR complexes with analysis of 885 CIDRα1 sequences, showing that the EPCR-binding surfaces of CIDRα1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRα1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.