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

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...

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Autores principales: Lopez, Andrea J., Andreadaki, Maria, Vahokoski, Juha, Deligianni, Elena, Calder, Lesley J., Camerini, Serena, Freitag, Anika, Bergmann, Ulrich, Rosenthal, Peter B., Sidén-Kiamos, Inga, Kursula, Inari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019781/
https://www.ncbi.nlm.nih.gov/pubmed/36877739
http://dx.doi.org/10.1371/journal.ppat.1011174
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author Lopez, Andrea J.
Andreadaki, Maria
Vahokoski, Juha
Deligianni, Elena
Calder, Lesley J.
Camerini, Serena
Freitag, Anika
Bergmann, Ulrich
Rosenthal, Peter B.
Sidén-Kiamos, Inga
Kursula, Inari
author_facet Lopez, Andrea J.
Andreadaki, Maria
Vahokoski, Juha
Deligianni, Elena
Calder, Lesley J.
Camerini, Serena
Freitag, Anika
Bergmann, Ulrich
Rosenthal, Peter B.
Sidén-Kiamos, Inga
Kursula, Inari
author_sort Lopez, Andrea J.
collection PubMed
description 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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spelling pubmed-100197812023-03-17 Structure and function of Plasmodium actin II in the parasite mosquito stages Lopez, Andrea J. Andreadaki, Maria Vahokoski, Juha Deligianni, Elena Calder, Lesley J. Camerini, Serena Freitag, Anika Bergmann, Ulrich Rosenthal, Peter B. Sidén-Kiamos, Inga Kursula, Inari PLoS Pathog Research Article 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. Public Library of Science 2023-03-06 /pmc/articles/PMC10019781/ /pubmed/36877739 http://dx.doi.org/10.1371/journal.ppat.1011174 Text en © 2023 Lopez et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lopez, Andrea J.
Andreadaki, Maria
Vahokoski, Juha
Deligianni, Elena
Calder, Lesley J.
Camerini, Serena
Freitag, Anika
Bergmann, Ulrich
Rosenthal, Peter B.
Sidén-Kiamos, Inga
Kursula, Inari
Structure and function of Plasmodium actin II in the parasite mosquito stages
title Structure and function of Plasmodium actin II in the parasite mosquito stages
title_full Structure and function of Plasmodium actin II in the parasite mosquito stages
title_fullStr Structure and function of Plasmodium actin II in the parasite mosquito stages
title_full_unstemmed Structure and function of Plasmodium actin II in the parasite mosquito stages
title_short Structure and function of Plasmodium actin II in the parasite mosquito stages
title_sort structure and function of plasmodium actin ii in the parasite mosquito stages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019781/
https://www.ncbi.nlm.nih.gov/pubmed/36877739
http://dx.doi.org/10.1371/journal.ppat.1011174
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