University of Oulu

Lopez AJ, Andreadaki M, Vahokoski J, Deligianni E, Calder LJ, Camerini S, et al. (2023) Structure and function of Plasmodium actin II in the parasite mosquito stages. PLoS Pathog 19(3): e1011174.

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

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Author: Lopez, Andrea J.1; Andreadaki, Maria2; Vahokoski, Juha1;
Organizations: 1Department of Biomedicine, University of Bergen, Bergen, Norway
2Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece
3Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, London, United Kingdom
4Istituto Superiore di Sanità, Roma, Italy
5Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.1 MB)
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Language: English
Published: Public Library of Science, 2023
Publish Date: 2023-09-11


Actins are filament-forming, highly-conserved proteins in eukaryotes. They are involved in essential processes in the cytoplasm and also have nuclear functions. Malaria parasites (Plasmodium spp.) have two actin isoforms that differ from each other and from canonical actins in structure and filament-forming properties. Actin I has an essential role in motility and is fairly well characterized. The structure and function of actin II are not as well understood, but mutational analyses have revealed two essential functions in male gametogenesis and in the oocyst. Here, we present expression analysis, high-resolution filament structures, and biochemical characterization of Plasmodium actin II. We confirm expression in male gametocytes and zygotes and show that actin II is associated with the nucleus in both stages in filament-like structures. Unlike actin I, actin II readily forms long filaments in vitro, and near-atomic structures in the presence or absence of jasplakinolide reveal very similar structures. Small but significant differences compared to other actins in the openness and twist, the active site, the D-loop, and the plug region contribute to filament stability. The function of actin II was investigated through mutational analysis, suggesting that long and stable filaments are necessary for male gametogenesis, while a second function in the oocyst stage also requires fine-tuned regulation by methylation of histidine 73. Actin II polymerizes via the classical nucleation-elongation mechanism and has a critical concentration of ~0.1 μM at the steady-state, like actin I and canonical actins. Similarly to actin I, dimers are a stable form of actin II at equilibrium.

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Series: PLoS pathogens
ISSN: 1553-7366
ISSN-E: 1553-7374
ISSN-L: 1553-7366
Volume: 19
Issue: 3
Article number: e1011174
DOI: 10.1371/journal.ppat.1011174
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This study was funded by grants from the Academy of Finland (310917 to IK), the Norwegian Research Council (262476 to IK), Sigrid Jusélius Foundation (to IK), Emil Aaltonen Foundation (to IK), Jane and Aatos Erkko Foundation (to IK), Fondation Sante, Greece (to ISK), State Scholarship Foundation IKY, Greece (MIS:5001552 to MA). PBR was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2106; PBR), the UK Medical Research Council (CC2106; PBR), and the Wellcome Trust (CC2106; PBR). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Academy of Finland Grant Number: 310917
Detailed Information: 310917 (Academy of Finland Funding decision)
Copyright information: © 2023 Lopez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.