2O02

Phosphorylation independent interactions between 14-3-3 and Exoenzyme S: from structure to pathogenesis

Summary for 2O02

• Entry DOI: 10.2210/pdb2o02/pdb
• Descriptor: 14-3-3 protein zeta/delta, ExoS (416-430) peptide, BENZOIC ACID, ... (4 entities in total)
• Functional Keywords: 14-3-3, adapter protein, exos, pathogen, protein binding-toxin complex, protein binding/toxin
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : P63104
• Total number of polymer chains: 4
• Total formula weight: 55612.74

Authors

Ottmann, C.,Yasmin, L.,Weyand, M.,Hauser, A.R.,Wittinghofer, A.,Hallberg, B. (deposition date: 2006-11-27, release date: 2007-11-27, Last modification date: 2023-12-27)

Primary citation

Ottmann, C.,Yasmin, L.,Weyand, M.,Veesenmeyer, J.L.,Diaz, M.H.,Palmer, R.H.,Francis, M.S.,Hauser, A.R.,Wittinghofer, A.,Hallberg, B.
Phosphorylation-independent interaction between 14-3-3 and exoenzyme S: from structure to pathogenesis
Embo J., 26:902-913, 2007

PubMed Abstract: 14-3-3 proteins are phosphoserine/phosphothreonine-recognizing adapter proteins that regulate the activity of a vast array of targets. There are also examples of 14-3-3 proteins binding their targets via unphosphorylated motifs. Here we present a structural and biological investigation of the phosphorylation-independent interaction between 14-3-3 and exoenzyme S (ExoS), an ADP-ribosyltransferase toxin of Pseudomonas aeruginosa. ExoS binds to 14-3-3 in a novel binding mode mostly relying on hydrophobic contacts. The 1.5 A crystal structure is supported by cytotoxicity analysis, which reveals that substitution of the corresponding hydrophobic residues significantly weakens the ability of ExoS to modify the endogenous targets RAS/RAP1 and to induce cell death. Furthermore, mutation of key residues within the ExoS binding site for 14-3-3 impairs virulence in a mouse pneumonia model. In conclusion, we show that ExoS binds 14-3-3 in a novel reversed orientation that is primarily dependent on hydrophobic residues. This interaction is phosphorylation independent and is required for the function of ExoS.

PubMed: 17235285
DOI: 10.1038/sj.emboj.7601530

Experimental method

X-RAY DIFFRACTION (1.5 Å)