The Duffy-Binding-Like β domain (DBLβ) of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant, PFD1235w, binds ICAM1
Publication: Research - peer-review › Conference abstract in proceedings – Annual report year: 2012
Plasmodium falciparum is by far the most virulent human malaria parasite. P. falciparum variant erythrocyte surface antigens, known as PfEMP1, play a crucial role in malaria pathogenesis as they mediate adhesion to host endothelial receptors. The PfEMP1 variant, PFD1235w, encoded by the 3D7 group A var gene has been associated with severe malaria and erythrocytes infected with parasites expressing PFD1235w binds ICAM1. To identify the PFD1235w domain(s) responsible for ICAM1 binding we used recombinant protein (NTS, CIDR1, DBL1-CIDR1, DBLdomains, CIDR2) and ICAM1 in Enzyme-Linked Immuno-Sorbent Assay (ELISA). We identified the DBLβ3-domain 4 (D4) of the PFD1235w to be responsible for ICAM1 binding in a concentration dependent manner and the binding could be inhibited by a panel of monoclonal ICAM1 antibodies. By using 3D protein modeling we generated different PfEMP1 hybrid molecules and truncated proteins in order to determine the essential binding region of the DBLβ3-D4 involved in the ICAM1 interaction. The hybrid molecules and truncated proteins were tested for ICAM1 binding in ELISA. Results indicate that the C-terminal of DBLβ3-D4 is directly involved in the ICAM1 interaction, while the N-terminal region is necessary for correct protein conformation. These results contribute to a greater understanding of how PfEMP1 interacts with endothelial receptors such as ICAM1 and provide a model for future analysis of other PfEMP1 variants adhering to ICAM1.
|Title||Joint Spring Symposium 2012 - Double burden of disease – how parasites interact with each other, their host and the society : Danish Society for Parasitology and Danish Society for Tropical Medicine & International Health|
|Publisher||Danish Society for Parasitology|
|Conference||Joint Spring Symposium 2012 : Danish Society for Parasitology and Danish Society for Tropical Medicine & International Health|
|Period||23/03/12 → …|
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