AI Article Synopsis
- 14-3-3 proteins are versatile adapter proteins that typically recognize phosphorylated targets, but they can also bind to some proteins without phosphorylation, such as the ExoS toxin from Pseudomonas aeruginosa.
- The study provides a detailed structural analysis, revealing that ExoS interacts with 14-3-3 primarily through hydrophobic contacts in a unique orientation.
- Disruption of this binding impacts ExoS's ability to modify critical proteins and diminishes its virulence in mouse models, highlighting the importance of this non-phosphorylated interaction for ExoS function.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794388 | PMC |
| http://dx.doi.org/10.1038/sj.emboj.7601530 | DOI Listing |
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