Details

Autor(en) / Beteiligte

• Robb, Craig S.
• Robb, Melissa
• Nano, Francis E.
• Boraston, Alisdair B.

Titel

The Structure of the Toxin and Type Six Secretion System Substrate Tse2 in Complex with Its Immunity Protein

Ist Teil von

• Structure (London), 2016-02, Vol.24 (2), p.277-284

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Tse2 is a cytoactive toxin secreted by a type six secretion apparatus of Pseudomonas aeruginosa. The Tse2 toxin naturally attacks a target in the cytoplasm of bacterial cells, and can cause toxicity if artificially introduced into eukaryotic cells. The X-ray crystal structure of the complex of Tse2 and its cognate immunity protein Tsi2 revealed a heterotetrameric structure with an extensive binding interface. Structural identity was found between Tse2 and NAD-dependent enzymes, especially ADP-ribosylating toxins, which facilitated the identification of the Tse2 active site and revealed it to be occluded upon binding the inhibitor Tsi2. The structural identity shared with NAD-dependent enzymes, including conserved catalytic residues, suggests that the mechanism of Tse2 toxicity may be NAD dependent. •Tse2 from P. aeruginosa has structural features similar to ADP-ribosylating toxins•The active-site of the Tse2 toxin is consistent with an NAD-dependent activity•Tse2 forms an inactivated heterotetrameric complex with the Tsi2 anti-toxin Tse2 is a Pseudomonas aeruginosa type 6 secretion system substrate and cytoactive toxin whose structural features suggest a relationship with ADP-ribosylating toxins and an active-site arrangement consistent with NAD-dependent activity, providing the first insight into the molecular basis of Tse2 toxicity.