The host targeting motif in exported Plasmodium proteins is cleaved in the parasite endoplasmic reticulum

Andrew R Osborne1, Kaye D Speicher, Pamela A Tamez

  • 1Center for Rare and Neglected Diseases, University of Notre Dame, 103 Galvin Life Sciences, South Bend, IN 46556, USA.

Insights

The malaria parasite

Area of Science:

  • Malariology
  • Molecular Parasitology
  • Cell Biology

Background:

  • The malaria parasite (Plasmodium) exports proteins to its host cell, the human erythrocyte, during its blood stage.
  • Many exported proteins utilize a conserved Plasmodium export element (PEXEL) motif for translocation.
  • The PEXEL motif is cleaved by an unknown protease during protein export.

Purpose of the Study:

  • To investigate the timing and location of PEXEL motif cleavage.
  • To determine if PEXEL cleavage is dependent on protein export into the host cell.

Main Methods:

  • Generated Plasmodium parasite lines expressing PEXEL-containing proteins targeted to different cellular compartments.
  • Analyzed PEXEL motif cleavage and N-acetylation in proteins retained within the parasite versus those exported.

Main Results:

  • Cleavage and N-acetylation of the PEXEL motif occurred efficiently even in proteins retained within the parasite's endoplasmic reticulum.
  • This indicates that PEXEL cleavage is not solely dependent on the export process into the host cell.

Conclusions:

  • PEXEL motif cleavage occurs early in the parasite's secretory pathway, specifically within the endoplasmic reticulum.
  • This finding provides crucial insights into the mechanism of protein export in malaria parasites.

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