A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq and Gi proteins

Nat Struct Mol Biol. 2013 Nov;20(11):1273-80. doi: 10.1038/nsmb.2688. Epub 2013 Oct 20.


Entomopathogenic Photorhabdus asymbiotica is an emerging pathogen in humans. Here, we identified a P. asymbiotica protein toxin (PaTox), which contains a glycosyltransferase and a deamidase domain. PaTox mono-O-glycosylates Y32 (or Y34) of eukaryotic Rho GTPases by using UDP-N-acetylglucosamine (UDP-GlcNAc). Tyrosine glycosylation inhibits Rho activation and prevents interaction with downstream effectors, resulting in actin disassembly, inhibition of phagocytosis and toxicity toward insects and mammalian cells. The crystal structure of the PaTox glycosyltransferase domain in complex with UDP-GlcNAc determined at 1.8-Å resolution represents a canonical GT-A fold and is the smallest glycosyltransferase toxin known. (1)H-NMR analysis identifies PaTox as a retaining glycosyltransferase. The glutamine-deamidase domain of PaTox blocks GTP hydrolysis of heterotrimeric Gαq/11 and Gαi proteins, thereby activating RhoA. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / metabolism*
  • Crystallography, X-Ray
  • Glycosylation
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Photorhabdus / enzymology*
  • Protein Conformation
  • Tyrosine / metabolism*
  • Uridine Diphosphate N-Acetylglucosamine / chemistry*
  • Uridine Diphosphate N-Acetylglucosamine / metabolism*
  • rho GTP-Binding Proteins / metabolism*


  • Bacterial Toxins
  • Tyrosine
  • Uridine Diphosphate N-Acetylglucosamine
  • rho GTP-Binding Proteins

Associated data

  • PDB/4MIX