title: Structural differences explain diverse functions of Plasmodium actins.
abstract: Actins are highly conserved proteins and key players in central processes in all eukaryotic cells. The two actins of the malaria parasite are among the most divergent eukaryotic actins and also differ from each other more than isoforms in any other species. Microfilaments have not been directly observed in Plasmodium and are presumed to be short and highly dynamic. We show that actin I cannot complement actin II in male gametogenesis, suggesting critical structural differences. Cryo-EM reveals that Plasmodium actin I has a unique filament structure, whereas actin II filaments resemble canonical F-actin. Both Plasmodium actins hydrolyze ATP more efficiently than α-actin, and unlike any other actin, both parasite actins rapidly form short oligomers induced by ADP. Crystal structures of both isoforms pinpoint several structural changes in the monomers causing the unique polymerization properties. Inserting the canonical D-loop to Plasmodium actin I leads to the formation of long filaments in vitro. In vivo, this chimera restores gametogenesis in parasites lacking actin II, suggesting that stable filaments are required for exflagellation. Together, these data underline the divergence of eukaryotic actins and demonstrate how structural differences in the monomers translate into filaments with different properties, implying that even eukaryotic actins have faced different evolutionary pressures and followed different paths for developing their polymerization properties.
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Vahokoski
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Saligram Prabhakar
authors.initials: SP
authors.lastname: Bhargav
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Ambroise
authors.initials: A
authors.lastname: Desfosses
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Heraklion, Crete, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Andreadaki
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Centre for Structural Systems Biology; Helmholtz Centre for Infection Research and German Electron Synchrotron, Hamburg, Germany.
authors.forename: Esa-Pekka
authors.initials: EP
authors.lastname: Kumpula
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Silvia Muñico
authors.initials: SM
authors.lastname: Martinez
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ignatev
authors.affiliation: Parasitology - Department of Infectious Diseases, University of Heidelberg Medical School, Heidelberg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Lepper
authors.affiliation: Parasitology - Department of Infectious Diseases, University of Heidelberg Medical School, Heidelberg, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Frischknecht
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Heraklion, Crete, Greece.
authors.forename: Inga
authors.initials: I
authors.lastname: Sidén-Kiamos
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Sachse
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Centre for Structural Systems Biology; Helmholtz Centre for Infection Research and German Electron Synchrotron, Hamburg, Germany.
authors.forename: Inari
authors.initials: I
authors.lastname: Kursula
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010962:Plasmodium berghei / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D015800:Protozoan Proteins
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