AMPylation of Rho GTPases by Vibrio VopS Disrupts Effector Binding and Downstream Signaling

Science. 2009 Jan 9;323(5911):269-72. doi: 10.1126/science.1166382. Epub 2008 Nov 27.

Abstract

The Vibrio parahaemolyticus type III effector VopS is implicated in cell rounding and the collapse of the actin cytoskeleton by inhibiting Rho guanosine triphosphatases (GTPases). We found that VopS could act to covalently modify a conserved threonine residue on Rho, Rac, and Cdc42 with adenosine 5'-monophosphate (AMP). The resulting AMPylation prevented the interaction of Rho GTPases with downstream effectors, thereby inhibiting actin assembly in the infected cell. Eukaryotic proteins were also directly modified with AMP, potentially expanding the repertoire of posttranslational modifications for molecular signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / metabolism*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Cell Shape
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Threonine / chemistry
  • Threonine / metabolism
  • Vibrio parahaemolyticus / metabolism*
  • Vibrio parahaemolyticus / pathogenicity
  • cdc42 GTP-Binding Protein / antagonists & inhibitors
  • cdc42 GTP-Binding Protein / chemistry
  • cdc42 GTP-Binding Protein / metabolism*
  • rac GTP-Binding Proteins / antagonists & inhibitors
  • rac GTP-Binding Proteins / chemistry
  • rac GTP-Binding Proteins / metabolism*
  • rho GTP-Binding Proteins / antagonists & inhibitors
  • rho GTP-Binding Proteins / chemistry
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Bacterial Proteins
  • Mutant Proteins
  • Recombinant Fusion Proteins
  • Threonine
  • Adenosine Monophosphate
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • rho GTP-Binding Proteins