Structural insights into Legionella RidL-Vps29 retromer subunit interaction reveal displacement of the regulator TBC1D5.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29146912.
- Also identified by DOI 10.1038/s41467-017-01512-5 and PMC identifier 5691146.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (RidL<sub>2-281</sub>) adopts a "foot-like" fold comprising a protruding β-hairpin at its "heel". The deletion of the β-hairpin, the exchange to Glu of Ile<sub>170</sub> in the β-hairpin, or Leu<sub>152</sub> in Vps29 abolishes the interaction in eukaryotic cells and in vitro. RidL<sub>2-281</sub> 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.
Medical subject headings
- Bacterial Proteins
- GTPase-Activating Proteins
- Legionella pneumophila
- Vesicular Transport Proteins