8A44

Plasmodium vivax Duffy binding protein region II bound the DARC ectodomain and monoclonal antibody DB1

Summary for 8A44

• Entry DOI: 10.2210/pdb8a44/pdb
• Descriptor: Duffy binding protein, Atypical chemokine receptor 1, Heavy chain of monoclonal antibody DB1, ... (5 entities in total)
• Functional Keywords: plasmodium vivax, malaria, reticulocyte invasion, duffy binding protein, darc, sulphotyrosine., cell adhesion
• Biological source: Plasmodium vivax (malaria parasite P. vivax); More
• Total number of polymer chains: 4
• Total formula weight: 88852.74

Authors

Moskovitz, R.,Higgins, M.K. (deposition date: 2022-06-10, release date: 2023-06-07, Last modification date: 2024-10-16)

Primary citation

Moskovitz, R.,Pholcharee, T.,DonVito, S.M.,Guloglu, B.,Lowe, E.,Mohring, F.,Moon, R.W.,Higgins, M.K.
Structural basis for DARC binding in reticulocyte invasion by Plasmodium vivax.
Nat Commun, 14:3637-3637, 2023

PubMed Abstract: The symptoms of malaria occur during the blood stage of infection, when the parasite replicates within human red blood cells. The human malaria parasite, Plasmodium vivax, selectively invades reticulocytes in a process which requires an interaction between the ectodomain of the human DARC receptor and the Plasmodium vivax Duffy-binding protein, PvDBP. Previous studies have revealed that a small helical peptide from DARC binds to region II of PvDBP (PvDBP-RII). However, it is also known that sulphation of tyrosine residues on DARC affects its binding to PvDBP and these residues were not observed in previous structures. We therefore present the structure of PvDBP-RII bound to sulphated DARC peptide, showing that a sulphate on tyrosine 41 binds to a charged pocket on PvDBP-RII. We use molecular dynamics simulations, affinity measurements and growth-inhibition experiments in parasites to confirm the importance of this interaction. We also reveal the epitope for vaccine-elicited growth-inhibitory antibody DB1. This provides a complete understanding of the binding of PvDBP-RII to DARC and will guide the design of vaccines and therapeutics to target this essential interaction.

PubMed: 37336887
DOI: 10.1038/s41467-023-39357-w

Experimental method

X-RAY DIFFRACTION (2.49 Å)