AI Article Synopsis
- Placental malaria is caused by infected red blood cells that adhere to the placenta through a specific protein interaction between Plasmodium falciparum and chondroitin sulfate proteoglycans.
- Human IgM antibodies bind to these proteins (PfEMP1), including the VAR2CSA variant, which helps to identify and potentially impact the malaria infection.
- A detailed cryo-electron microscopy study shows how VAR2CSA binds to IgM in a way that limits its interaction with its receptor, thereby affecting the attachment of infected erythrocytes to the placenta.
Article Abstract
Placental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) adhering to chondroitin sulfate proteoglycans in placenta via VAR2CSA-type PfEMP1. Human pentameric immunoglobulin M (IgM) binds to several types of PfEMP1, including VAR2CSA via its Fc domain. Here, a 3.6 Å cryo-electron microscopy map of the IgM-VAR2CSA complex reveals that two molecules of VAR2CSA bind to the Cµ4 of IgM through their DBL3X and DBL5ε domains. The clockwise and anti-clockwise rotation of the two VAR2CSA molecules on opposite faces of IgM juxtaposes C-termini of both VAR2CSA near the J chain, where IgM creates a wall between both VAR2CSA molecules and hinders its interaction with its receptor. To support this, we show when VAR2CSA is bound to IgM, its staining on IEs as well as binding of IEs to chondroitin sulfate A in vitro is severely compromised.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570280 | PMC |
| http://dx.doi.org/10.1038/s41467-023-41838-x | DOI Listing |
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