Structure and function of Plasmodium actin II in the parasite mosquito stages

Andrea J Lopez1, Maria Andreadaki2, Juha Vahokoski1

  • 1Department of Biomedicine, University of Bergen, Bergen, Norway.

Plos Pathogens
|March 6, 2023
PubMed

Insights

Plasmodium actin II, crucial for malaria parasite reproduction, forms stable filaments essential for male gametogenesis and oocyst development. Its structure and function are key to understanding parasite biology.

Area of Science:

  • Molecular Biology
  • Parasitology
  • Structural Biology

Background:

  • Actins are essential eukaryotic proteins involved in cellular processes.
  • Malaria parasites (Plasmodium spp.) possess two unique actin isoforms, actin I and actin II.
  • Actin II's structure and function, particularly in gametogenesis and oocyst development, remain less understood compared to actin I.

Purpose of the Study:

  • To elucidate the structure, filament formation, and biochemical properties of Plasmodium actin II.
  • To investigate the essential functions of actin II in male gametogenesis and the oocyst stage.
  • To understand the structural basis for actin II's filament stability and functional regulation.

Main Methods:

  • Expression analysis in Plasmodium gametocytes and zygotes.
  • High-resolution structural determination of actin II filaments.
  • Biochemical characterization, including in vitro filament formation and polymerization kinetics.
  • Mutational analysis to probe functional requirements, including histidine 73 methylation.

Main Results:

  • Actin II is expressed in male gametocytes and zygotes, localizing to filament-like structures near the nucleus.
  • Actin II readily forms long, stable filaments in vitro, with near-atomic structures revealing subtle differences from canonical actins.
  • Mutational studies indicate stable actin II filaments are vital for male gametogenesis, while oocyst function depends on methylation of histidine 73.
  • Actin II polymerization follows a classical nucleation-elongation mechanism with a critical concentration of ~0.1 μM.

Conclusions:

  • Plasmodium actin II possesses unique structural features contributing to filament stability, essential for its roles in parasite development.
  • Actin II's functions in male gametogenesis and oocyst development are critical for parasite survival and transmission.
  • Fine-tuned regulation, including methylation, is crucial for actin II's diverse functions within the malaria parasite lifecycle.

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