The phytotoxin fusicoccin differently regulates 14-3-3 proteins association to mode III targets

Abstract

Modulation of the interaction of regulatory 14-3-3 proteins to their physiological partners through small cell-permeant molecules is a promising strategy to control cellular processes where 14-3-3s are engaged. Here, we show that the fungal phytotoxin fusicoccin (FC), known to stabilize 14-3-3 association to the plant plasma membrane H(+) -ATPase, is able to stabilize 14-3-3 interaction to several client proteins with a mode III binding motif. Isothermal titration calorimetry analysis of the interaction between 14-3-3s and different peptides reproducing a mode III binding site demonstrated the FC ability to stimulate 14-3-3 the association. Moreover, molecular docking studies provided the structural rationale for the differential FC effect, which exclusively depends on the biochemical properties of the residue in peptide C-terminal position. Our study proposes FC as a promising tool to control cellular processes regulated by 14-3-3 proteins, opening new perspectives on its potential pharmacological applications.

Keywords: 14-3-3 proteins; drug discovery; fusicoccin; molecular docking; protein-protein interaction.