Structural Insights into the Pseudomonas aeruginosa Type VI Virulence Effector Tse1 Bacteriolysis and Self-protection Mechanisms

Abstract

Background: Pseudomonas aeruginosa employs Tse1 to kill rival cells and Tsi1 to inactivate Tse1 for self-protection. Results: Tse1 features a conserved catalytic site for murein hydrolysis, and Tsi1 specifically occupies the substrate-binding sites of Tse1. Conclusion: Tse1 acts as a murein peptidase, and Tsi1 blocks its substrate binding. Significance: This work builds a novel understanding of niche competition among bacteria.

Structure of the Type VI Effector-Immunity Complex (Tae4-Tai4) Provides Novel Insights into the Inhibition Mechanism of the Effector by Its Immunity Protein*

“…3B). The third catalytic residue, Cys-110 in Tae1, is not essential for the cleavage of the D-Glu-mDAP bond (8,9). However, the Asp-139 of Tae4, which is equivalent to the third active site, appears to affect enzyme activity.…”

“…Dimerization of Tai4-Tai4 is composed of six ␣-helices, whereas Tai1 displays an all ␤ fold (7,9). The Tai4 dimerization occurs mainly through the interaction of ␣2, ␣3, and ␣5 of both monomers (Fig.…”

“…9A). Previous studies have shown that the insertion of ␤h-␤i loop into the catalytic cleft is critical for inhibition (7,9). The substrate binding sites are occupied by the ␤h-␤i loop, Ser-107 of which shows a remarkable binding affinity to Tae1.…”

“…Our group and others have solved the crystal structures Tae1 and its complex with Tai1 from P. aeruginosa and revealed the structural mechanisms for the inhibition of Tae1 by Tai1 (7)(8)(9)(10). But so far the structure of Tae4 has not been reported.…”

Identification, Structure, and Function of a Novel Type VI Secretion Peptidoglycan Glycoside Hydrolase Effector-Immunity Pair

“…Cell wall-degrading T6S effectors distribute into two groups: those that act as amidases, cleaving the peptidoglycan molecule within its peptide stems and cross-links and those that act as glycoside hydrolases, cleaving the glycan backbone of the molecule. T6S amidase effectors have been studied extensively (3,9,10,(12)(13)(14)(15). The enzymes are broadly distributed among Proteobacteria and form four phylogenetically distinct families that constitute the Tae (type IV secretion amidase effector) superfamily.…”