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Structural Differences Explain Diverse Functions of Actins


Malaria parasites have two actin isoforms, which are among the most divergent within the actin family that comprises highly conserved proteins, essential in all eukaryotic cells. In Plasmodium, actin is indispensable for motility and, thus, the infectivity of the deadly parasite. Yet, actin filaments have not been observed in vivo in these pathogens. Here, we show that the two Plasmodium actins differ from each other in both monomeric and filamentous form and that actin I cannot replace actin II during male gametogenesis. Whereas the major isoform actin I cannot form stable filaments alone, the mosquito-stage-specific actin II readily forms long filaments that have dimensions similar to canonical actins. A chimeric actin I mutant that forms long filaments in vitro also rescues gametogenesis in parasites lacking actin II. Both Plasmodium actins rapidly hydrolyze ATP and form short oligomers in the presence of ADP, which is a fundamental difference to all other actins characterized to date. Structural and functional differences in the two Plasmodium actin isoforms compared both to each other and to canonical actins reveal how the polymerization properties of eukaryotic actins have evolved along different avenues.


Vyšlo v časopise: Structural Differences Explain Diverse Functions of Actins. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004091
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004091

Souhrn

Malaria parasites have two actin isoforms, which are among the most divergent within the actin family that comprises highly conserved proteins, essential in all eukaryotic cells. In Plasmodium, actin is indispensable for motility and, thus, the infectivity of the deadly parasite. Yet, actin filaments have not been observed in vivo in these pathogens. Here, we show that the two Plasmodium actins differ from each other in both monomeric and filamentous form and that actin I cannot replace actin II during male gametogenesis. Whereas the major isoform actin I cannot form stable filaments alone, the mosquito-stage-specific actin II readily forms long filaments that have dimensions similar to canonical actins. A chimeric actin I mutant that forms long filaments in vitro also rescues gametogenesis in parasites lacking actin II. Both Plasmodium actins rapidly hydrolyze ATP and form short oligomers in the presence of ADP, which is a fundamental difference to all other actins characterized to date. Structural and functional differences in the two Plasmodium actin isoforms compared both to each other and to canonical actins reveal how the polymerization properties of eukaryotic actins have evolved along different avenues.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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