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Nat Commun. 2017 Nov 16;8(1):1543. doi: 10.1038/s41467-017-01512-5.

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

Author information

1
Institute of Medical Microbiology, University of Zürich, Gloriastrasse 30, 8006, Zürich, Switzerland.
2
UMR5235, DIMNP, CNRS/Université Montpellier, Place Eugène Bataillon, Montpellier, 34095, cedex 5, France.
3
Institute of Medical Microbiology, University of Zürich, Gloriastrasse 30, 8006, Zürich, Switzerland. m.seeger@imm.uzh.ch.
4
Institute of Medical Microbiology, University of Zürich, Gloriastrasse 30, 8006, Zürich, Switzerland. hilbi@imm.uzh.ch.

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.

PMID:
29146912
PMCID:
PMC5691146
DOI:
10.1038/s41467-017-01512-5
[Indexed for MEDLINE]
Free PMC Article

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