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Structural insights into Legionella RidL-Vps29 retromer subunit interaction reveal displacement of the regulator TBC1D5

Author

Listed:
  • Kevin Bärlocher

    (Institute of Medical Microbiology, University of Zürich)

  • Cedric A. J. Hutter

    (Institute of Medical Microbiology, University of Zürich)

  • A. Leoni Swart

    (Institute of Medical Microbiology, University of Zürich)

  • Bernhard Steiner

    (Institute of Medical Microbiology, University of Zürich)

  • Amanda Welin

    (Institute of Medical Microbiology, University of Zürich)

  • Michael Hohl

    (Institute of Medical Microbiology, University of Zürich)

  • François Letourneur

    (UMR5235, DIMNP, CNRS/Université Montpellier)

  • Markus A. Seeger

    (Institute of Medical Microbiology, University of Zürich)

  • Hubert Hilbi

    (Institute of Medical Microbiology, University of Zürich)

Abstract

Legionella pneumophila can cause Legionnaires’ disease and replicates intracellularly in a distinct Legionella-containing vacuole (LCV). LCV formation is a complex process that involves a plethora of type IV-secreted effector proteins. The effector RidL binds the Vps29 retromer subunit, blocks retrograde vesicle trafficking, and promotes intracellular bacterial replication. Here, we reveal that the 29-kDa N-terminal domain of RidL (RidL2–281) adopts a “foot-like” fold comprising a protruding β-hairpin at its “heel”. The deletion of the β-hairpin, the exchange to Glu of Ile170 in the β-hairpin, or Leu152 in Vps29 abolishes the interaction in eukaryotic cells and in vitro. RidL2–281 or RidL displace the Rab7 GTPase-activating protein (GAP) TBC1D5 from the retromer and LCVs, respectively, and TBC1D5 promotes the intracellular growth of L. pneumophila. Thus, the hydrophobic β-hairpin of RidL is critical for binding of the L. pneumophila effector to the Vps29 retromer subunit and displacement of the regulator TBC1D5.

Suggested Citation

  • Kevin Bärlocher & Cedric A. J. Hutter & A. Leoni Swart & Bernhard Steiner & Amanda Welin & Michael Hohl & François Letourneur & Markus A. Seeger & Hubert Hilbi, 2017. "Structural insights into Legionella RidL-Vps29 retromer subunit interaction reveal displacement of the regulator TBC1D5," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01512-5
    DOI: 10.1038/s41467-017-01512-5
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