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Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b

Author

Listed:
  • Marietta S. Kaspers

    (University Medical Centre Hamburg-Eppendorf (UKE))

  • Vivian Pogenberg

    (University Medical Centre Hamburg-Eppendorf (UKE))

  • Christian Pett

    (Umeå University)

  • Stefan Ernst

    (Technical University of Munich)

  • Felix Ecker

    (Technical University of Munich)

  • Philipp Ochtrop

    (Umeå University)

  • Michael Groll

    (Technical University of Munich)

  • Christian Hedberg

    (Umeå University)

  • Aymelt Itzen

    (University Medical Centre Hamburg-Eppendorf (UKE)
    University Medical Centre Hamburg-Eppendorf (UKE))

Abstract

Bacterial pathogens often make use of post-translational modifications to manipulate host cells. Legionella pneumophila, the causative agent of Legionnaires disease, secretes the enzyme AnkX that uses cytidine diphosphate-choline to post-translationally modify the human small G-Protein Rab1 with a phosphocholine moiety at Ser76. Later in the infection, the Legionella enzyme Lem3 acts as a dephosphocholinase, hydrolytically removing the phosphocholine. While the molecular mechanism for Rab1 phosphocholination by AnkX has recently been resolved, structural insights into the activity of Lem3 remained elusive. Here, we stabilise the transient Lem3:Rab1b complex by substrate mediated covalent capture. Through crystal structures of Lem3 in the apo form and in complex with Rab1b, we reveal Lem3’s catalytic mechanism, showing that it acts on Rab1 by locally unfolding it. Since Lem3 shares high structural similarity with metal-dependent protein phosphatases, our Lem3:Rab1b complex structure also sheds light on how these phosphatases recognise protein substrates.

Suggested Citation

  • Marietta S. Kaspers & Vivian Pogenberg & Christian Pett & Stefan Ernst & Felix Ecker & Philipp Ochtrop & Michael Groll & Christian Hedberg & Aymelt Itzen, 2023. "Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37621-7
    DOI: 10.1038/s41467-023-37621-7
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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Joel Fauser & Burak Gulen & Vivian Pogenberg & Christian Pett & Danial Pourjafar-Dehkordi & Christoph Krisp & Dorothea Höpfner & Gesa König & Hartmut Schlüter & Matthias J. Feige & Martin Zacharias & , 2021. "Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Yunhao Tan & Zhao-Qing Luo, 2011. "Legionella pneumophila SidD is a deAMPylase that modifies Rab1," Nature, Nature, vol. 475(7357), pages 506-509, July.
    4. Alyssa Ingmundson & Anna Delprato & David G. Lambright & Craig R. Roy, 2007. "Legionella pneumophila proteins that regulate Rab1 membrane cycling," Nature, Nature, vol. 450(7168), pages 365-369, November.
    5. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    6. Jiqing Du & Marie-Kristin von Wrisberg & Burak Gulen & Matthias Stahl & Christian Pett & Christian Hedberg & Kathrin Lang & Sabine Schneider & Aymelt Itzen, 2021. "Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    7. Shaeri Mukherjee & Xiaoyun Liu & Kohei Arasaki & Justin McDonough & Jorge E. Galán & Craig R. Roy, 2011. "Modulation of Rab GTPase function by a protein phosphocholine transferase," Nature, Nature, vol. 477(7362), pages 103-106, September.
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