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Issue 9, 2014
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Comparative study of Plasmodium falciparum erythrocyte membrane protein 1-DBLα domain variants with respect to antigenic variations and docking interaction analysis with glycosaminoglycans

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Abstract

The variant surface antigen PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) encoded by the polymorphic multi-copy var gene family plays an important role in parasite biology and the host–parasite interactions. Sequestration and antigenic variation is an essential component in the survival and pathogenesis of Plasmodium falciparum and contributes to chronic infection. The DBLα domain of PfEMP1 is a potential target for immuno-epidemiological studies and has been visualized as a vaccine candidate against severe malaria. Specific host receptors like heparin, heparan sulphate, blood group A and complement receptor 1 have been reported to bind the DBLα domain. Although heparin has been experimentally shown to disrupt the parasite–host interaction and effectively disrupt rosetting, the binding sites for the DBLα domain and the mechanism behind heparin-mediated rosette inhibition have not been elucidated. In this study, 3D structures and epitopes of the DBLα domain in 3D7 and in two Indian isolates have been predicted and compared. We have carried out docking studies on DBLα domains with human GAG receptors (heparin and heparan sulphate) to predict the strength of association between the protein–ligand interactions. The DBLα domain structures showed extensive diversity and polymorphism in their binding sites. The docking results indicate that heparin binds more effectively with high affinity as compared to heparan sulphate with some common interacting residues. These common residues can play an important role in rosetting and will aid in the designing of inhibitors specific to the interactions between DBLα and heparin or heparan sulphate would be important in malaria treatment. Thus it may lead to the development of novel interference strategies to block red blood cell invasion and provide protection against malaria.

Graphical abstract: Comparative study of Plasmodium falciparum erythrocyte membrane protein 1-DBLα domain variants with respect to antigenic variations and docking interaction analysis with glycosaminoglycans

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Publication details

The article was received on 06 May 2014, accepted on 20 Jun 2014 and first published on 04 Jul 2014


Article type: Paper
DOI: 10.1039/C4MB00274A
Author version available: Download Author version (PDF)
Citation: Mol. BioSyst., 2014,10, 2466-2479
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    Comparative study of Plasmodium falciparum erythrocyte membrane protein 1-DBLα domain variants with respect to antigenic variations and docking interaction analysis with glycosaminoglycans

    M. R. Agrawal, A. D. Ozarkar, S. Gupta, D. N. Deobagkar and D. D. Deobagkar, Mol. BioSyst., 2014, 10, 2466
    DOI: 10.1039/C4MB00274A

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