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VopA inhibits ATP binding by acetylating the catalytic loop of MAPK kinases

Jennifer E Trosky1, Yan Li, Sohini Mukherjee

  • 1Department of Molecular Biology, Protein Chemistry Technology Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.

The Journal of Biological Chemistry
|September 21, 2007
PubMed

Insights

The bacterial effector VopA from Vibrio parahemeolyticus inhibits mitogen-activated protein kinase (MAPK) signaling by acetylating kinases. This novel mechanism blocks ATP binding, inactivating the signaling pathway during infection.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Bacterial pathogens like Vibrio parahemeolyticus employ type III effectors to manipulate host signaling pathways.
  • Mitogen-activated protein kinase (MAPK) signaling is crucial for cellular responses and is a target for pathogen manipulation.

Purpose of the Study:

  • To elucidate the mechanism by which the Vibrio parahemeolyticus effector VopA inhibits MAPK signaling.
  • To identify the specific target and molecular action of VopA.

Main Methods:

  • Biochemical assays to characterize VopA's enzymatic activity.
  • Analysis of kinase activity and protein acetylation.
  • Investigation of VopA's interaction with MAPK kinases (MKKs).

Main Results:

  • VopA functions as an acetyltransferase, inhibiting MAPK signaling.
  • VopA acetylates a conserved lysine residue in the catalytic loop of MKKs.
  • Acetylation prevents ATP binding, rendering MKKs inactive and blocking downstream signaling.

Conclusions:

  • VopA employs a novel mechanism to inhibit MAPK signaling by targeting MKKs.
  • This study reveals a new regulatory role for lysine acetylation in controlling enzyme activity.
  • Understanding VopA's mechanism provides insights into host-pathogen interactions and kinase regulation.

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