Structure of a pathogen effector reveals the enzymatic mechanism of a novel acetyltransferase family

Nat Struct Mol Biol. 2016 Sep;23(9):847-52. doi: 10.1038/nsmb.3279. Epub 2016 Aug 15.


Effectors secreted by the type III secretion system are essential for bacterial pathogenesis. Members of the Yersinia outer-protein J (YopJ) family of effectors found in diverse plant and animal pathogens depend on a protease-like catalytic triad to acetylate host proteins and produce virulence. However, the structural basis for this noncanonical acetyltransferase activity remains unknown. Here, we report the crystal structures of the YopJ effector HopZ1a, produced by the phytopathogen Pseudomonas syringae, in complex with the eukaryote-specific cofactor inositol hexakisphosphate (IP6) and/or coenzyme A (CoA). Structural, computational and functional characterizations reveal a catalytic core with a fold resembling that of ubiquitin-like cysteine proteases and an acetyl-CoA-binding pocket formed after IP6-induced structural rearrangements. Modeling-guided mutagenesis further identified key IP6-interacting residues of Salmonella effector AvrA that are required for acetylating its substrate. Our study reveals the structural basis of a novel class of acetyltransferases and the conserved allosteric regulation of YopJ effectors by IP6.

MeSH terms

  • Acetylation
  • Acetyltransferases / chemistry*
  • Allosteric Regulation
  • Arabidopsis Proteins / chemistry*
  • Bacterial Proteins / chemistry*
  • Catalytic Domain
  • Coenzyme A / chemistry
  • Crystallography, X-Ray
  • Host-Pathogen Interactions
  • Hydrogen Bonding
  • Models, Molecular
  • Phytic Acid / chemistry
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Interaction Domains and Motifs
  • Protein Processing, Post-Translational
  • Pseudomonas syringae / enzymology


  • Arabidopsis Proteins
  • Bacterial Proteins
  • Phytic Acid
  • Acetyltransferases
  • Coenzyme A