ArticleThe Journal of biological chemistry2012
Structural and functional insight into how the Plasmodium falciparum VAR2CSA protein mediates binding to chondroitin sulfate A in placental malaria.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.
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Who cites it
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.
- Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review.BMC medicine · 2020Pooled it
- Placental malaria caused by Plasmodium vivax or P. falciparum in Colombia: Histopathology and mediators in placental processes.PloS one · 2022Trial
- Kinetics of B cell responses to Plasmodium falciparum erythrocyte membrane protein 1 in Ghanaian women naturally exposed to malaria parasites.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Chondroitin sulfate shapes the unfolded protein response in osteosarcoma to sustain cancer cell survival during ER stress.Cell death & disease · 2026Article
- Coarse-Grained Martini 3 Model of Chondroitin Sulfate A.Journal of chemical theory and computation · 2026Article
- VAR2CSA-specific IgG and IgM antibodies are markers of exposure and protection against adverse malaria pregnancy outcomes.Malaria journal · 2025Article
- Protein catenation potentiates antitumor activity of malaria VAR2CSA navigation CAR-T cells in a mouse model of hematological malignancies.Journal for immunotherapy of cancer · 2025Article
- Fc-Afucosylation of VAR2CSA-Specific Immunoglobulin G and Clinical Immunity to Placental Plasmodium falciparum Malaria.The Journal of infectious diseases · 2025Article
- Combining rVAR2 and Anti-EpCAM to Increase the Capture Efficiency of Non-Small-Cell Lung Cancer Cell Lines in the Flow Enrichment Target Capture Halbach (FETCH) Magnetic Separation System.International journal of molecular sciences · 2024Article
- Structure-guided design of VAR2CSA-based immunogens and a cocktail strategy for a placental malaria vaccine.PLoS pathogens · 2024Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Variable Surface Antigens ofProtein and peptide letters · 2024Review
- Mechanical forces control the valency of the malaria adhesin VAR2CSA by exposing cryptic glycan binding sites.PLoS computational biology · 2023Article
- Review
- Aotus nancymaae model predicts human immune response to the placental malaria vaccine candidate VAR2CSA.Lab animal · 2023Article
- Knobs, Adhesion, and Severe Falciparum Malaria.Tropical medicine and infectious disease · 2023Review
- A conformational epitope in placental malaria vaccine antigen VAR2CSA: What does it teach us?PLoS pathogens · 2023Article
- A novel enemy of cancer: recent investigations into protozoan anti-tumor properties.Frontiers in cellular and infection microbiology · 2023Review
- The delayed bloodstream clearance ofFrontiers in cellular and infection microbiology · 2023Article
- A conserved epitope in VAR2CSA is targeted by a cross-reactive antibody originating fromFrontiers in cellular and infection microbiology · 2023Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malaria is a major global health problem. Pregnant women are susceptible to infection regardless of previously acquired immunity. Placental malaria is caused by parasites capable of sequestering in the placenta. This is mediated by VAR2CSA, a parasite antigen that interacts with chondroitin sulfate A (CSA). One vaccine strategy is to block this interaction with VAR2CSA-specific antibodies. It is a priority to define a small VAR2CSA fragment that can be used in an adhesion blocking vaccine. In this, the obvious approach is to define regions of VAR2CSA involved in receptor binding. It has been shown that full-length recombinant VAR2CSA binds specifically to CSA with nanomolar affinity, and that the CSA-binding site lies in the N-terminal part of the protein. In this study we define the minimal binding region by truncating VAR2CSA and analyzing CSA binding using biosensor technology. We show that the core CSA-binding site lies within the DBL2X domain and parts of the flanking interdomain regions. This is in contrast to the idea that single domains do not possess the structural requirements for specific CSA binding. Small-angle x-ray scattering measurements enabled modeling of VAR2CSA and showed that the CSA-binding DBL2X domain is situated in the center of the structure. Mutating classic sulfate-binding sites in VAR2CSA, along with testing dependence of ionic interactions, suggest that the CSA binding is not solely dependent on the sulfated CSA structure. Based on these novel PfEMP1 structure-function studies, we have constructed a small VAR2CSA antigen that has the capacity to induce highly adhesion-blocking antibodies.
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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.