3BQI

Structure of a chondroitin sulphate binding DBL3X from a var2csa encoded PfEMP1 protein

3BQI の概要

• エントリーDOI: 10.2210/pdb3bqi/pdb
• 関連するPDBエントリー: 3BQK 3BQL
• 分子名称: Erythrocyte membrane protein 1, GLYCEROL (3 entities in total)
• 機能のキーワード: malaria, pregnancy, pfemp1, var2csa, dbl3x, chondroitin sulphate, cell adhesion
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41255.41

構造登録者

Higgins, M.K. (登録日: 2007-12-20, 公開日: 2008-06-24, 最終更新日: 2024-10-30)

主引用文献

Higgins, M.K.
The structure of a chondroitin sulfate-binding domain important in placental malaria.
J.Biol.Chem., 283:21842-21846, 2008

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: 18550531
DOI: 10.1074/jbc.C800086200

実験手法

X-RAY DIFFRACTION (2.2 Å)