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Actin activates Pseudomonas aeruginosa ExoY nucleotidyl cyclase toxin and ExoY-like effector domains from MARTX toxins

Author

Listed:
  • Alexander Belyy

    (Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires
    Gamaleya Research Center)

  • Dorothée Raoux-Barbot

    (Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires)

  • Cosmin Saveanu

    (Institut Pasteur, CNRS UMR3525, Génétique des Interactions Macromoléculaires)

  • Abdelkader Namane

    (Institut Pasteur, CNRS UMR3525, Génétique des Interactions Macromoléculaires)

  • Vasily Ogryzko

    (Institut Gustave Roussy, CNRS UMR 8126, Unité de Signaling, Nuclei and Innovations in Oncology)

  • Lina Worpenberg

    (Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires)

  • Violaine David

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay)

  • Veronique Henriot

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay)

  • Souad Fellous

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay)

  • Christien Merrifield

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay)

  • Elodie Assayag

    (Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires)

  • Daniel Ladant

    (Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires)

  • Louis Renault

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay)

  • Undine Mechold

    (Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires)

Abstract

The nucleotidyl cyclase toxin ExoY is one of the virulence factors injected by the Pseudomonas aeruginosa type III secretion system into host cells. Inside cells, it is activated by an unknown eukaryotic cofactor to synthesize various cyclic nucleotide monophosphates. ExoY-like adenylate cyclases are also found in Multifunctional-Autoprocessing Repeats-in-ToXin (MARTX) toxins produced by various Gram-negative pathogens. Here we demonstrate that filamentous actin (F-actin) is the hitherto unknown cofactor of ExoY. Association with F-actin stimulates ExoY activity more than 10,000 fold in vitro and results in stabilization of actin filaments. ExoY is recruited to actin filaments in transfected cells and alters F-actin turnover. Actin also activates an ExoY-like adenylate cyclase MARTX effector domain from Vibrio nigripulchritudo. Finally, using a yeast genetic screen, we identify actin mutants that no longer activate ExoY. Our results thus reveal a new sub-group within the class II adenylyl cyclase family, namely actin-activated nucleotidyl cyclase (AA-NC) toxins.

Suggested Citation

  • Alexander Belyy & Dorothée Raoux-Barbot & Cosmin Saveanu & Abdelkader Namane & Vasily Ogryzko & Lina Worpenberg & Violaine David & Veronique Henriot & Souad Fellous & Christien Merrifield & Elodie Ass, 2016. "Actin activates Pseudomonas aeruginosa ExoY nucleotidyl cyclase toxin and ExoY-like effector domains from MARTX toxins," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13582
    DOI: 10.1038/ncomms13582
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    Cited by:

    1. Alexander Belyy & Philipp Heilen & Philine Hagel & Oliver Hofnagel & Stefan Raunser, 2023. "Structure and activation mechanism of the Makes caterpillars floppy 1 toxin," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Alexander Belyy & Felipe Merino & Undine Mechold & Stefan Raunser, 2021. "Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens," Nature Communications, Nature, vol. 12(1), pages 1-9, December.

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