ArticleProceedings of the National Academy of Sciences of the United States of America2010
Full-length extracellular region of the var2CSA variant of PfEMP1 is required for specific, high-affinity binding to CSA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
92 citing papers in PubMed, 152 citations in OpenAlex.
- Antibody reactivity to the VAR2CSA DBL5 domain among pregnant women in Northern Ghana.BMC infectious diseases · 2026Article
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- Casein Kinases 2-dependent phosphorylation of the placental ligand VAR2CSA regulates Plasmodium falciparum-infected erythrocytes cytoadhesion.PLoS pathogens · 2025Article
- Do Blood group and Sickle cell trait protect against placental malaria?Journal of public health in Africa · 2023Article
- Mechanical forces control the valency of the malaria adhesin VAR2CSA by exposing cryptic glycan binding sites.PLoS computational biology · 2023Article
- A conserved epitope in VAR2CSA is targeted by a cross-reactive antibody originating fromFrontiers in cellular and infection microbiology · 2023Article
- Red Blood Cells Oligosaccharides as Targets for Plasmodium Invasion.Biomolecules · 2022Review
- An Invariant Protein That Colocalizes With VAR2CSA on Plasmodium falciparum-Infected Red Cells Binds to Chondroitin Sulfate A.The Journal of infectious diseases · 2022Article
- Live Vaccination with Blood-StageVaccines · 2022Article
- Monoclonal antibodies for malaria prevention.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Expression of Large Full-Length PfEMP1 Proteins in HEK293 Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Allelic variants of full-length VAR2CSA, the placental malaria vaccine candidate, differ in antigenicity and receptor binding affinity.Communications biology · 2021Article
- Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination.Nature communications · 2021Article
- Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding.Nature communications · 2021Article
- Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA.Nature microbiology · 2021Article
- Progress and Insights Toward an Effective Placental Malaria Vaccine.Frontiers in immunology · 2021Review
- Reduction of pl-CSA through ChSy-2 knockout inhibits tumorigenesis and metastasis of choriocarcinoma in JEG3 cells.International journal of medical sciences · 2021Article
- Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding.The Journal of biological chemistry · 2020Article
- Effectiveness of Sulfadoxine-Pyrimethamine for Intermittent Preventive Treatment of Malaria and Adverse Birth Outcomes in Pregnant Women.Pathogens (Basel, Switzerland) · 2020Article
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pregnancy-associated malaria (PAM) is a serious consequence of sequestration of Plasmodium falciparum-parasitized erythrocytes (PE) in the placenta through adhesion to chondroitin sulfate A (CSA) present on placental proteoglycans. Recent work implicates var2CSA, a member of the PfEMP1 family, as the mediator of placental sequestration and as a key target for PAM vaccine development. Var2CSA is a 350 kDa transmembrane protein, whose extracellular region includes six Duffy-binding-like (DBL) domains. Due to its size and high cysteine content, the full-length var2CSA extracellular region has not hitherto been expressed in heterologous systems, thus limiting investigations to individual recombinant domains. Here we report for the first time the expression of the full-length var2CSA extracellular region (domains DBL1X to DBL6epsilon) from the 3D7 parasite strain using the human embryonic kidney 293 cell line. We show that the recombinant extracellular var2CSA region is correctly folded and that, unlike the individual DBL domains, it binds with high affinity and specificity to CSA (K(D) = 61 nM) and efficiently inhibits PE from binding to CSA. Structural characterization by analytical ultracentrifugation and small-angle x-ray scattering reveals a compact organization of the full-length protein, most likely governed by specific interdomain interactions, rather than an extended structure. Collectively, these data suggest that a high-affinity, CSA-specific binding site is formed by the higher-order structure of the var2CSA extracellular region. These results have important consequences for the development of an effective vaccine and therapeutic inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.