The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family.

Autor: Kundu P; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK., Naskar D; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK., McKie SJ; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK., Dass S; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Kanjee U; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Introini V; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.; Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK., Ferreira MU; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.; Global Health and Tropical Medicine, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Institute of Hygiene and Tropical Medicine, NOVA University of Lisbon, Lisbon, Portugal., Cicuta P; Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK., Duraisingh M; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. mduraisi@hsph.harvard.edu., Deane JE; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. jed55@cam.ac.uk., Rayner JC; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. jcr1003@cam.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Sep 14; Vol. 14 (1), pp. 5703. Date of Electronic Publication: 2023 Sep 14.
DOI: 10.1038/s41467-023-40885-8
Abstrakt: 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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