3BQL
Structure of a chondroitin sulphate binding DBL3X domain from a var2csa encoded PfEMP1 protein
Summary for 3BQL
| Entry DOI | 10.2210/pdb3bql/pdb |
| Related | 3BQI 3BQK |
| Descriptor | Erythrocyte membrane protein 1, SULFATE ION, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | malaira, preganacy, var2csa encoded pfemp1 protein dbl3x domain, chondroitin sulphate a, cell adhesion |
| Biological source | Plasmodium falciparum |
| Total number of polymer chains | 1 |
| Total formula weight | 41351.48 |
| Authors | Higgins, M.K. (deposition date: 2007-12-20, release date: 2008-06-24, Last modification date: 2024-10-16) |
| Primary citation | Higgins, M.K. The structure of a chondroitin sulfate-binding domain important in placental malaria. J.Biol.Chem., 283:21842-21846, 2008 Cited by PubMed Abstract: Adhesive PfEMP1 proteins are displayed on the surface of malaria-infected red blood cells. They play a critical role in the disease, tethering infected cells away from destruction by the spleen and causing many severe symptoms. A molecular understanding of how these domains maintain their binding properties while evading immune detection will be important in developing therapeutics. In malaria of pregnancy, domains from the var2csa-encoded PfEMP1 protein interact with chondroitin sulfate on the placenta surface. This causes accumulation of infected red blood cells, leading to placental inflammation and block of blood flow to the developing fetus. This is associated with maternal anemia, low birth weight, and premature delivery and can lead to the death of mother and child. Here I present the structure of the chondroitin sulfate-binding DBL3X domain from a var2csa-encoded PfEMP1 protein. The domain adopts a fold similar to malarial invasion proteins, with extensive loop insertions. One loop is flexible in the unliganded structure but observed in the presence of sulfate or disaccharide, where it completes a sulfate-binding site. This loop, and others surrounding this putative carbohydrate-binding site, are flexible and polymorphic, perhaps protecting the binding site from immune detection. This suggests a model for how the domain maintains ligand binding while evading the immune response and will guide future drug and vaccine development. PubMed: 18550531DOI: 10.1074/jbc.C800086200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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