Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502043/
https://www.ncbi.nlm.nih.gov/pubmed/37709739
http://dx.doi.org/10.1038/s41467-023-40885-8
_version_ 1785106233453182976
author 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.
author_facet 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.
author_sort Kundu, Prasun
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10502043
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-105020432023-09-16 The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family 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. Nat Commun Article 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. Nature Publishing Group UK 2023-09-14 /pmc/articles/PMC10502043/ /pubmed/37709739 http://dx.doi.org/10.1038/s41467-023-40885-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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.
The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family
title The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family
title_full The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family
title_fullStr The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family
title_full_unstemmed The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family
title_short The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family
title_sort structure of a plasmodium vivax tryptophan rich antigen domain suggests a lipid binding function for a pan-plasmodium multi-gene family
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502043/
https://www.ncbi.nlm.nih.gov/pubmed/37709739
http://dx.doi.org/10.1038/s41467-023-40885-8
work_keys_str_mv AT kunduprasun thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT naskardeboki thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT mckieshannonj thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT dasssheena thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT kanjeeusheer thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT introiniviola thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT ferreiramarcelou thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT cicutapietro thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT duraisinghmanoj thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT deanejanete thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT raynerjulianc thestructureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT kunduprasun structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT naskardeboki structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT mckieshannonj structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT dasssheena structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT kanjeeusheer structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT introiniviola structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT ferreiramarcelou structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT cicutapietro structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT duraisinghmanoj structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT deanejanete structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily
AT raynerjulianc structureofaplasmodiumvivaxtryptophanrichantigendomainsuggestsalipidbindingfunctionforapanplasmodiummultigenefamily