Structural basis for DARC binding in reticulocyte invasion by Plasmodium vivax.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 06 2023
19 06 2023
Historique:
received:
28
02
2023
accepted:
06
06
2023
medline:
21
6
2023
pubmed:
20
6
2023
entrez:
19
6
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37336887
doi: 10.1038/s41467-023-39357-w
pii: 10.1038/s41467-023-39357-w
pmc: PMC10279640
doi:
Substances chimiques
Antigens, Protozoan
0
Duffy Blood-Group System
0
Protozoan Proteins
0
Tyrosine
42HK56048U
ACKR1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3637Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M021157/1
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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