Abstract
Human receptor gC1qR is a 32 kD protein that mediates the cytoadherence of Plasmodium falciparum-infected erythrocytes (IEs) to human brain microvascular endothelial cells (HBMEC) and platelets. The cytoadherence of IEs to gC1qR has been associated with severe malaria symptoms. The cytoadherence to gC1qR is mediated by the Duffy binding-like β12 (DBLβ12) domain of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), PFD0020c. Here, we report the structural insights into the binding of the DBLβ12 domain of PfEMP1 with the human receptor gC1qR using computational methods. A molecular model of the DBLβ12 domain was generated and used for protein–protein docking with the host receptor gC1qR. The protein–protein docking revealed that the DBLβ12 asymmetrically interacts with two subunits of the gC1qR trimer at the solution face of gC1qR. A total of 21 amino acid residues of DBLβ12 interact with 26 amino acid residues in the gC1qR trimer through 99 nonbonding interactions and 4 hydrogen bonds. Comparative analysis of binding sites on the DBL domain fold for the two receptors gC1qR and ICAM1 showed that the two sites are distinct. This is the first study that provides structural insights into DBLβ12 binding with its receptor gC1qR and may help in designing novel antisevere malaria interventions.
Highlights
Malaria is one of the most devastating parasitic diseases
This study has identified and characterized molecular interaction between gC1qR
Duffy binding-like β12 (DBLβ12) of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) PFD0020c of P. falciparum 3D7 using computational methods. This is the first study to characterize the structural details of gC1qR–DBLβ12 interaction in malaria
Summary
Malaria is one of the most devastating parasitic diseases. Malaria has caused about409,000 deaths in 2019. Malaria is one of the most devastating parasitic diseases. An estimated 67% of all malaria deaths are among children under. 5 years of age [1]. Most of the malaria related deaths are caused by Plasmodium falciparum infections, 5 species of Plasmodium are known to cause human malaria. The P. falciparum infected erythrocytes (IEs) have the unique ability to cytoadhere to host cells and completely sequester in the blood vasculature of the human host. The P. falciparuminfected erythrocytes may form rosettes and clumps when they cytoadhere to uninfected erythrocytes and platelets, respectively. The P. falciparum-infected erythrocytes can bind and adhere to microvascular endothelial cells and sequester in the blood vasculature
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