Yersinia protein kinase YopO is activated by a novel G-actin binding process

J Biol Chem. 2007 Jan 26;282(4):2268-77. doi: 10.1074/jbc.M610071200. Epub 2006 Nov 22.


Pathogenic bacteria of the genus Yersinia employ a type III secretion system to inject effector proteins (Yops) into host cells. The Yops down-regulate host cell functions through unique biochemical activities. YopO, a serine/threonine kinase required for Yersinia virulence, is activated by host cell actin via an unknown process. Here we show that YopO kinase is activated by formation of a 1:1 complex with monomeric (G) actin but is unresponsive to filamentous (F) actin. Two separate G-actin binding sites, one in the N-terminal kinase region (amino acids 89-440) and one in the C-terminal guanine nucleotide dissociation inhibitor-like region (amino acids 441-729) of YopO, were identified. Actin binding to both of these sites was necessary for effective autophosphorylation of YopO on amino acids Ser-90 and Ser-95. A S90A/S95A YopO mutant was strongly reduced in substrate phosphorylation, suggesting that autophosphorylation activates YopO kinase activity. In cells the kinase activity of YopO regulated rounding/arborization and was specifically required for inhibition of Yersinia YadA-dependent phagocytosis. Thus, YopO kinase is activated by a novel G-actin binding process, and this appears to be crucial for its anti-host cell functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Cell Line
  • Enzyme Activation
  • Humans
  • Mutation
  • Phosphorylation
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Substrate Specificity
  • Up-Regulation
  • Yersinia / enzymology*
  • Yersinia / pathogenicity
  • Yersinia Infections / metabolism
  • Yersinia Infections / microbiology*


  • Actins
  • Bacterial Proteins
  • YopO protein, Yersinia enterocolitica
  • Protein Serine-Threonine Kinases