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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Dictyostelium
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Legionella pneumophila / metabolism*
  • Legionella pneumophila / physiology
  • Mice
  • Microscopy, Confocal
  • Models, Molecular
  • Protein Binding
  • Protein Domains
  • Protein Transport
  • RAW 264.7 Cells
  • Vacuoles / metabolism
  • Vacuoles / microbiology
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / metabolism*


  • Bacterial Proteins
  • GTPase-Activating Proteins
  • TBC1D5 protein, human
  • VPS29 protein, human
  • Vesicular Transport Proteins