RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity

Mol Cell. 2009 Dec 25;36(6):1060-72. doi: 10.1016/j.molcel.2009.11.014.


Prenylated Rab proteins exist in the cytosol as soluble, high-affinity complexes with GDI that need to be disrupted for membrane attachment and targeting of Rab proteins. The Legionella pneumophila protein DrrA displaces GDI from Rab1:GDI complexes, incorporating Rab1 into Legionella-containing vacuoles and activating Rab1 by exchanging GDP for GTP. Here, we present the crystal structure of a complex between the GEF domain of DrrA and Rab1 and a detailed kinetic analysis of this exchange. DrrA efficiently catalyzes nucleotide exchange and mimics the general nucleotide exchange mechanism of mammalian GEFs for Ras-like GTPases. We show that the GEF activity of DrrA is sufficient to displace prenylated Rab1 from the Rab1:GDI complex. Thus, apparent GDI displacement by DrrA is linked directly to nucleotide exchange, suggesting a basic model for GDI displacement and specificity of Rab localization that does not require discrete GDI displacement activity.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Guanine Nucleotide Dissociation Inhibitors / metabolism*
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Guanosine Diphosphate / metabolism*
  • Guanosine Triphosphate / metabolism*
  • Humans
  • Legionella pneumophila / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Protein Conformation
  • rab1 GTP-Binding Proteins / chemistry
  • rab1 GTP-Binding Proteins / genetics
  • rab1 GTP-Binding Proteins / metabolism*


  • Bacterial Proteins
  • DNA-Binding Proteins
  • DrrA protein, Bacteria
  • Guanine Nucleotide Dissociation Inhibitors
  • Guanine Nucleotide Exchange Factors
  • Multiprotein Complexes
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • rab1 GTP-Binding Proteins

Associated data

  • PDB/3JZ9
  • PDB/3JZA