ArticleNature communications2021
Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Malaria and cancer: common features and interactions.Trends in parasitology · 2026Review
- Targeting protein-protein interactions in Plasmodium: from asexual replication to sexual development.Parasites & vectors · 2026Review
- Coarse-Grained Martini 3 Model of Chondroitin Sulfate A.Journal of chemical theory and computation · 2026Article
- Radical footprinting in mammalian whole blood.Nature communications · 2026Article
- 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
- Machine learning framework to extract physicochemical features of B-cell epitopes recognized by a cross-reactive antibody.NPJ systems biology and applications · 2025Article
- Hydroxyl and Trifluoromethyl Radical Carbohydrate Footprinting for Probing Protein Binding Components of Oligosaccharides.Analytical chemistry · 2025Article
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- Fc-Afucosylation of VAR2CSA-Specific Immunoglobulin G and Clinical Immunity to Placental Plasmodium falciparum Malaria.The Journal of infectious diseases · 2025Article
- Targeting Oncofoetal Chondroitin Sulphate Allows Identification of Tumour-Derived Extracellular Vesicles.Journal of extracellular vesicles · 2025Article
- Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate.NPJ precision oncology · 2025Article
- Heparan-6-O-endosulfatase 2, a cancer-related proteoglycan enzyme, is effectively inhibited by a specific sea cucumber fucosylated glycosaminoglycan.Glycobiology · 2025Article
- Markers of neutrophil activation and some immune and haematological indices in malaria infection during pregnancy.BMC immunology · 2025Article
- Identification ofFrontiers in immunology · 2025Article
- Malaria vaccines: a new era of prevention and control.Nature reviews. Microbiology · 2024Review
- Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate.Nature communications · 2024Article
- Accurate model and ensemble refinement using cryo-electron microscopy maps and Bayesian inference.PLoS computational biology · 2024Article
- Structure-guided design of VAR2CSA-based immunogens and a cocktail strategy for a placental malaria vaccine.PLoS pathogens · 2024Article
- The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates forBiomolecules · 2024Review
- Variable Surface Antigens ofProtein and peptide letters · 2024Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 3 countries.
Funding
Abstract
Placental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Here, we report cryo-EM structures of the VAR2CSA ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization. Notably, the surface displays a single significantly electropositive patch, compatible with binding of negatively charged CS. Using molecular docking and molecular dynamics simulations as well as comparative hydroxyl radical protein foot-printing of VAR2CSA in complex with placental CS, we identify the CS-binding groove, intersecting with the positively charged patch of the central VAR2CSA structure. We identify distinctive conserved structural features upholding the macro-molecular domain complex and CS binding capacity of VAR2CSA as well as divergent elements possibly allowing immune escape at or near the CS binding site. These observations will support rational design of second-generation placental malaria vaccines.
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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.