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Cited by 14Malaria Research and ControlEnzyme Structure and FunctionErythrocyte Function and Pathophysiology

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

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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.·2023·Nature Communications
DOI 10.1038/s41467-023-40885-8PMC PMC10502043

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Abstract

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.

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Metadata

Authors
Kundu, P., Naskar, D., McKie, S. J., Dass, S., Kanjee, U., Introini, V., Ferreira, M. U., Cicuta, P., Duraisingh, M., Deane, J. E., & Rayner, J. C.
Affiliations
  • University of Cambridge (GB)
  • Harvard University (US)
  • University of Lisbon (PT)
Corresponding author
  • Duraisingh, Manoj
  • Deane, Janet E.
  • Rayner, Julian C.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-09-14
Volume
14
Issue
1
Pages
5703-5703
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-40885-8
PMC
PMC10502043
OpenAlex
W4386736732
Cited by
14
References
4
Citations by year
2026: 3 · 2025: 6 · 2024: 5
FWCI
3.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Wellcome Trust (222323/Z/21/Z, 219447/Z/19/Z)
  • U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R01AI137154)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Health Sciences › Medicine › Physiology (medical) › Erythrocyte Function and Pathophysiology
Keywords
Plasmodium vivax, merozoite surface protein, lipid binding, reticulocyte invasion, red blood cell binding, glycosphingolipids, crystal structure
MeSH terms
Antigens, Protozoan, Humans, Plasmodium, Plasmodium vivax, Sulfoglycosphingolipids, Tryptophan, Malaria, Vivax

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