Molecular and Biochemical Parasitology
Posted on Friday, 20 April 2012

Identification of a specific region of Plasmodium falciparum EBL-1 that binds to host receptor glycophorin B and inhibits merozoite invasion in human Feature Article

Molecular and Biochemical Parasitology, Volume 183, Issue 1, May 2012, Pages 23-31
Xuerong Li, Marina Marinkovic, Crystal Russo, C James McKnight, Theresa L Coetzer, Athar H Chishti

Identification of a specific region of Plasmodium falciparum EBL-1 that binds to host receptor glycophorin B and inhibits merozoite invasion in human

The malaria parasite Plasmodium falciparum invades human erythrocytes through multiple pathways utilizing several ligand–receptor interactions. These interactions are broadly classified in two groups according to their dependency on sialic acid residues. Here, we focus on the sialic acid-dependent pathway by using purified glycophorins and red blood cells (RBCs) to screen a cDNA phage display library derived from P. falciparum FCR3 strain, a sialic acid-dependent strain. This screen identified several parasite proteins including the erythrocyte-binding ligand-1, EBL-1. The phage cDNA insert encoded the 69-amino acid peptide, termed F2i, which is located within the F2 region of the DBL domain, designated here as D2, of EBL-1. Recombinant D2 and F2i polypeptides bound to purified glycophorins and RBCs, and the F2i peptide was found to interfere with binding of D2 domain to its receptor. Both D2 and F2i polypeptides bound to trypsin-treated but not neuraminidase or chymotrypsin-treated erythrocytes, consistent with known glycophorin B resistance to trypsin, and neither the D2 nor F2i polypeptide bound to glycophorin B-deficient erythrocytes. Importantly, purified D2 and F2i polypeptides partially inhibited merozoite reinvasion in human erythrocytes. Our results show that the host erythrocyte receptor glycophorin B directly interacts with the DBL domain of parasite EBL-1, and the core binding site is contained within the 69 amino acid F2i region (residues 601–669) of the DBL domain. Together, these findings suggest that a recombinant F2i peptide with stabilized structure could provide a protective function at blood stage infection and represents a valuable addition to a multi-subunit vaccine against malaria.
 

Click here to view full text

Search
Register with Malaria Nexus for:
Free Articles & Latest Reviews
Email Alerts
Podcasts and Webinars
Register Now!
Members Sign In
Forgotten your password?
Elsevier
Copyright © 2014 Elsevier B.V. All rights reserved | Terms & Conditions | Privacy Policy

Cookies are set by this site. To decline them or learn more, visit our cookies page.