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14-3-3 proteins are required for the inhibition of Ras by exoenzyme S

M L Henriksson1, U Trollér, B Hallberg

  • 1Cellular and Molecular Biology, University of Umeâ, S-901 87 Umeâ, Sweden.

The Biochemical Journal
|July 21, 2000
PubMed

Insights

14-3-3 proteins bind unphosphorylated ligands like ExoS, which is crucial for ExoS

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Microbiology

Background:

  • 14-3-3 proteins are crucial regulators involved in signal transduction and cell cycle checkpoint control.
  • These proteins typically bind to phosphoserine-containing motifs on target proteins.
  • However, interactions with unphosphorylated proteins, such as bacterial toxins, are also known.

Purpose of the Study:

  • To identify the specific interaction site of 14-3-3 proteins on Pseudomonas aeruginosa exoenzyme S (ExoS).
  • To investigate the functional significance of the 14-3-3/ExoS interaction in vivo.
  • To determine the role of this interaction in ExoS-mediated Ras inactivation and virulence.

Main Methods:

  • Identification of the ExoS binding site for 14-3-3 proteins.
  • In vivo and in vitro experiments to confirm the interaction between ExoS and 14-3-3.
  • Assessment of ExoS's ADP-ribosyltransferase activity on Ras and its impact on bacterial virulence.

Main Results:

  • The study identified the specific interaction site on ExoS for 14-3-3 proteins.
  • The interaction between ExoS and 14-3-3 was confirmed to occur in vivo.
  • Disruption of the 14-3-3 binding site on ExoS impaired its ability to ADP-ribosylate Ras and reduced its virulence.

Conclusions:

  • 14-3-3 proteins bind to unphosphorylated ExoS, a mechanism distinct from their canonical phosphoserine-dependent interactions.
  • This interaction is essential for ExoS-mediated inactivation of Ras, a key host cell regulator.
  • Targeting the 14-3-3 binding site on ExoS represents a potential strategy to inhibit its virulence.

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