Legionella pneumophila SidD is a deAMPylase that modifies Rab1

Nature. 2011 Jul 6;475(7357):506-9. doi: 10.1038/nature10307.


Legionella pneumophila actively modulates host vesicle trafficking pathways to facilitate its intracellular replication with effectors translocated by the Dot/Icm type IV secretion system (T4SS). The SidM/DrrA protein functions by locking the small GTPase Rab1 into an active form by its guanine nucleotide exchange factor (GEF) and AMPylation activity. Here we demonstrate that the L. pneumophila protein SidD preferably deAMPylates Rab1. We found that the deAMPylation activity of SidD could suppress the toxicity of SidM to yeast and is required to release Rab1 from bacterial phagosomes efficiently. A molecular mechanism for the temporal control of Rab1 activity in different phases of L. pneumophila infection is thus established. These observations indicate that AMPylation-mediated signal transduction is a reversible process regulated by specific enzymes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aspartic Acid / chemistry
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Proteins / toxicity
  • Cells, Cultured
  • Female
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Guanine Nucleotide Exchange Factors / toxicity
  • Legionella pneumophila / enzymology*
  • Legionnaires' Disease / enzymology*
  • Legionnaires' Disease / physiopathology
  • Macrophages / enzymology
  • Macrophages / pathology
  • Mice
  • Phenotype
  • Plasmids / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Time Factors
  • Transformation, Genetic
  • rab1 GTP-Binding Proteins / metabolism*


  • Bacterial Proteins
  • Guanine Nucleotide Exchange Factors
  • SidD protein, Legionella pneumophila
  • SidM protein, Legionella pneumophila
  • Aspartic Acid
  • rab1 GTP-Binding Proteins