Last Updated: 02/10/2025
Structural studies of reticulocyte invasion in Plasmodium vivax
Objectives
The objectives of this study are to:
- structurally characterise the ectodomain of PvDBP (PvDBPecto) using cryogenic electron microscopy (cryo-EM), alone and bound to full-length DARC;
- determine whether functional antibodies bind regions outside PvDBP-RII, by raising serum from rats immunized with PvDBPecto and assessing using growth inhibition assays (GIA) in P. knowlesi; and
- find binding partners for PkDBPβ/γ and regions of PvDBP outside RII to better understand the biology of Plasmodium invasion of red blood cells.
The blood stage of malaria causes the clinical symptoms of the disease. In P. vivax the machinery for invading red blood cells depends on the essential interaction between the P.vivax Duffy Binding Protein (PvDBP) and the Duffy Antigen Receptor for Chemokines (DARC)(1)(2)(3). Recent studies have shown how the N-terminal peptide of DARC binds to the PvDBP binding domain RII (PvDBP- RII)(4)(5)(6), and how a few acquired and vaccine-elicited antibodies bind PvDBP-RII (6)(7)(8). PvDBP however has other domains which remain uncharacterised, and a full-length structure with DARC, together with functional characterization, would provide a deeper understanding of the interaction.
Oct 2024 — Sep 2027
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