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

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 ?-hairpin at its "heel". The deletion of the ?-hairpin, the exchange to Glu of Ile170 in the ?-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 ?-hairpin of RidL is critical for binding of the L. pneumophila effector to the Vps29 retromer subunit and displacement of the regulator TBC1D5.

SUBMITTER: Barlocher K 

PROVIDER: S-EPMC5691146 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature