The essential malaria protein PfCyRPA targets glycans to invade erythrocytes

Christopher J Day1, Paola Favuzza2, Sabrina Bielfeld3

  • 1Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia.

Cell Reports
|April 4, 2024
PubMed

Insights

Plasmodium falciparum cysteine-rich protective antigen (PfCyRPA) is a lectin that binds to specific human cell surface sugars. Targeting this lectin activity offers a new strategy against malaria.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Immunology

Background:

  • Plasmodium falciparum causes severe malaria.
  • PfCyRPA is crucial for erythrocyte invasion but its role is unclear.

Purpose of the Study:

  • To elucidate the function of PfCyRPA in malaria parasite invasion.
  • To investigate PfCyRPA as a potential therapeutic target.

Main Methods:

  • Molecular modeling to predict PfCyRPA lectin sites.
  • Mutagenesis studies to validate binding sites.
  • Development of transgenic parasite lines for functional analysis.

Main Results:

  • PfCyRPA functions as a lectin, specifically binding α2-6-linked N-acetylneuraminic acid (Neu5Ac).
  • Demonstrated a >50-fold preference for human Neu5Ac over non-human forms.
  • Mutant PfCyRPA lacking lectin activity impaired parasite invasion.
  • Inhibition of PfCyRPA lectin activity reduced parasite multiplication.

Conclusions:

  • PfCyRPA's lectin activity is essential for Plasmodium falciparum invasion.
  • Targeting PfCyRPA lectin activity presents a promising strategy for malaria treatment and prevention.
  • Potential for drug development, immunotherapy, and vaccines targeting PfCyRPA.

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