Author(s):
Kundu, Prasun ; Naskar, Deboki ; McKie, Shannon J ; Dass, Sheena ; Kanjee, Usheer ; Introini, Viola ; Ferreira, Marcelo U ; Cicuta, Pietro ; Duraisingh, Manoj ; Deane, Janet E ; Rayner, Julian C
Date: 2023
Persistent ID: http://hdl.handle.net/10362/160091
Origin: Repositório Institucional da UNL
Subject(s): Humans; Plasmodium vivax/genetics; Tryptophan; Plasmodium; Antigens, Protozoan/genetics; Malaria, Vivax; Sulfoglycosphingolipids; QR Microbiology; QD Chemistry; QR180 Immunology; Parasitology; Infectious Diseases; Biochemistry, Genetics and Molecular Biology(all); SDG 3 - Good Health and Well-being
Description
© 2023. Springer Nature Limited.
Tryptophan Rich Antigens (TRAgs) are encoded by a multi-gene family found in all Plasmodium species, but are significantly expanded in P. vivax and closely related parasites. We show that multiple P. vivax TRAgs are expressed on the merozoite surface and that one, PVP01_0000100 binds red blood cells with a strong preference for reticulocytes. Using X-ray crystallography, we solved the structure of the PVP01_0000100 C-terminal tryptophan rich domain, which defines the TRAg family, revealing a three-helical bundle that is conserved across Plasmodium and has structural homology with lipid-binding BAR domains involved in membrane remodelling. Biochemical assays confirm that the PVP01_0000100 C-terminal domain has lipid binding activity with preference for sulfatide, a glycosphingolipid present in the outer leaflet of plasma membranes. Deletion of the putative orthologue in P. knowlesi, PKNH_1300500, impacts invasion in reticulocytes, suggesting a role during this essential process. Together, this work defines an emerging molecular function for the Plasmodium TRAg family.
