Seminar with Herwig Schüler

Herwig Schüler
Karolinska Institute, Stockholm

14-3-3 protein mediated activation of ExoS,
an early toxin in Pseudomonas infection

Abstract: ADP-ribosylating toxins of invasive bacteria modify host proteins to prepare the host cell for bacterial invasion. We have solved crystal structures of Pseudomonas aeruginosa exotoxins-S and -T in complex with 14-3-3, the host protein that activates these toxins. Along with biochemical evidence, our results reveal that rather than inducing the formation of a functional active site, 14-3-3 proteins act as exotoxin chaperones. Furthermore, the crystal structures revealed an extensive hydrophobic interface between the exotoxins and their essential chaperone. An organic compound was found to block that interface and inhibit toxin activity. This encourages the development of protein protein interaction inhibitors to combat Pseudomonas, a multiresistant pathogen of major importance in clinical environments.

Herwig Schüler is a great speaker and focuses in his research on ADP-ribosylation - understanding the enzymes involved (bacterial toxins and PARP family enzymes) and developing compounds to inhibit their activities.