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Malaria parasites use a soluble RhopH complex for erythrocyte invasion and an integral form for nutrient uptake

Marc A Schureck1, Joseph E Darling2, Alan Merk2

  • 1Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States.

Elife
|January 4, 2021
PubMed

Insights

Malaria parasites

Area of Science:

  • Parasitology
  • Molecular Biology
  • Structural Biology

Background:

  • The RhopH complex is crucial for malaria parasite invasion and nutrient uptake.
  • The specific interactions and trafficking of RhopH complex proteins remain uncharacterized.

Purpose of the Study:

  • To elucidate the structure and trafficking mechanism of the Plasmodium RhopH complex.
  • To understand how the RhopH complex facilitates host cell invasion and nutrient transport.

Main Methods:

  • Single-particle cryo-electron microscopy (cryo-EM) at 2.9 Å resolution.
  • Biochemical analysis of protein complex assembly and stoichiometry.
  • Investigating protein trafficking through host cell membranes.

Main Results:

  • The RhopH complex is synthesized as a soluble 1:1:1 stoichiometric assembly of CLAG3, RhopH2, and RhopH3.
  • The complex traffics across the vacuolar membrane and integrates into the erythrocyte membrane via the PTEX translocon.
  • Cryo-EM reveals extensive interactions between CLAG3 and other subunits, with shielded transmembrane helices.

Conclusions:

  • The RhopH complex is a large, stable assembly optimized for trafficking.
  • The complex undergoes large-scale rearrangements for host membrane insertion, similar to other pore-forming proteins.
  • Understanding RhopH complex structure and function is key to developing new malaria control strategies.
Keywords:
P. falciparumcryo-EMerythrocyte invasioninfectious diseasemalariamicrobiologymolecular biophysicsnutrient uptakepore-forming proteinsprotein structurestructural biology

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