title: 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.
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Paiardini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Aducci
authors.forename: Laura
authors.initials: L
authors.lastname: Cervoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Cutruzzolà
authors.forename: Cristina
authors.initials: C
authors.lastname: Di Lucente
authors.forename: Giacomo
authors.initials: G
authors.lastname: Janson
authors.forename: Stefano
authors.initials: S
authors.lastname: Pascarella
authors.forename: Serena
authors.initials: S
authors.lastname: Rinaldo
authors.forename: Sabina
authors.initials: S
authors.lastname: Visconti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Camoni
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002151:Calorimetry; D002462:Cell Membrane / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009183:Mycotoxins / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*; D006180:Proton-Translocating ATPases / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D053651:Receptors, Interleukin-9 / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D048948:14-3-3 Proteins; C436291:CDKN1B protein, human; C103539:GPR15 protein, human; D006027:Glycosides; C096896:HAP1 protein, human; D009183:Mycotoxins; D009419:Nerve Tissue Proteins; D010748:Phosphopeptides; D024683:Potassium Channels, Tandem Pore Domain; D043562:Receptors, G-Protein-Coupled; D053651:Receptors, Interleukin-9; D018000:Receptors, Peptide; D050760:Cyclin-Dependent Kinase Inhibitor p27; C420132:potassium channel subfamily K member 3; C007808:fusicoccin; C446530:phospholipase D delta; D010739:Phospholipase D; D006180:Proton-Translocating ATPases
keywords: 14-3-3 proteins; drug discovery; fusicoccin; molecular docking; protein-protein interaction