Evolutionarily divergent, unstable filamentous actin is essential for gliding motility in apicomplexan parasites

PLoS Pathogens
Kristen M SkillmanL D Sibley

Abstract

Apicomplexan parasites rely on a novel form of actin-based motility called gliding, which depends on parasite actin polymerization, to migrate through their hosts and invade cells. However, parasite actins are divergent both in sequence and function and only form short, unstable filaments in contrast to the stability of conventional actin filaments. The molecular basis for parasite actin filament instability and its relationship to gliding motility remain unresolved. We demonstrate that recombinant Toxoplasma (TgACTI) and Plasmodium (PfACTI and PfACTII) actins polymerized into very short filaments in vitro but were induced to form long, stable filaments by addition of equimolar levels of phalloidin. Parasite actins contain a conserved phalloidin-binding site as determined by molecular modeling and computational docking, yet vary in several residues that are predicted to impact filament stability. In particular, two residues were identified that form intermolecular contacts between different protomers in conventional actin filaments and these residues showed non-conservative differences in apicomplexan parasites. Substitution of divergent residues found in TgACTI with those from mammalian actin resulted in formation of longer, m...Continue Reading

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Methods Mentioned

BETA
electron microscopy
light scattering
fluorescence microscopy
light
transgenic
X-ray
PCR

Related Concepts

NSC 613009
Isoactin
Cell Motility
Microfilaments
Parasites
Phalloidine
Phylogeny
Episomes
Plasmodium
Toxoplasma gondii

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