Journal
LIFE-BASEL
Volume 11, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/life11090993
Keywords
malaria; cytoadherence; gC1qR; Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1); Duffy binding-like (DBL) domain
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Funding
- National Science, Technology and Innovation Plan (MAARIFAH) [14-MED2474-10]
- King Abdul-Aziz City for Science and Technology (KACST), Kingdom of Saudi Arabia
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This study provides structural insights into the binding of the PfEMP1 DBL beta 12 domain with the human receptor gC1qR, potentially aiding in the development of novel interventions for severe malaria.
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 beta 12 (DBL beta 12) domain of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), PFD0020c. Here, we report the structural insights into the binding of the DBL beta 12 domain of PfEMP1 with the human receptor gC1qR using computational methods. A molecular model of the DBL beta 12 domain was generated and used for protein-protein docking with the host receptor gC1qR. The protein-protein docking revealed that the DBL beta 12 asymmetrically interacts with two subunits of the gC1qR trimer at the solution face of gC1qR. A total of 21 amino acid residues of DBL beta 12 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 DBL beta 12 binding with its receptor gC1qR and may help in designing novel antisevere malaria interventions.
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