title: The Structure of the Toxin and Type Six Secretion System Substrate Tse2 in Complex with Its Immunity Protein.
abstract: 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.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 3P6, Canada.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Robb
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 3P6, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Robb
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 3P6, Canada.
authors.forename: Francis E
authors.initials: FE
authors.lastname: Nano
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 3P6, Canada. Electronic address: boraston@uvic.ca.
authors.forename: Alisdair B
authors.initials: AB
authors.lastname: Boraston
mesh_terms: D036002:ADP Ribose Transferases / Q000737:chemistry; D000595:Amino Acid Sequence; D000992:Antitoxins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D036002:ADP Ribose Transferases