7tvh | pdb_00007tvh
Hyperlytic variant of Tae1, Type VI secretion amidase effector 1, from Pseudomonas aeruginosa (Cys110Ser)
Structural highlights
FunctionTSE1_PSEAE Toxin secreted by the H1 type VI (H1-T6SS) secretion system into the periplasm of recipient cells. Degrades peptidoglycan via amidase activity thereby helping itself to compete with other bacteria (PubMed:21776080, PubMed:22700987, PubMed:22813741, PubMed:22931054). To protect itself, the bacterium synthesizes immunity protein Tsi1 that specifically interacts with and inactivates cognate toxin (PubMed:21776080, PubMed:22700987, PubMed:22931054).[1] [2] [3] [4] Publication Abstract from PubMedMembers of the bacterial T6SS amidase effector (Tae) superfamily of toxins are delivered between competing bacteria to degrade cell wall peptidoglycan. Although Taes share a common substrate, they exhibit distinct antimicrobial potency across different competitor species. To investigate the molecular basis governing these differences, we quantitatively defined the functional determinants of Tae1 from Pseudomonas aeruginosa PAO1 using a combination of nuclear magnetic resonance and a high-throughput in vivo genetic approach called deep mutational scanning (DMS). As expected, combined analyses confirmed the role of critical residues near the Tae1 catalytic center. Unexpectedly, DMS revealed substantial contributions to enzymatic activity from a much larger, ring-like functional hot spot extending around the entire circumference of the enzyme. Comparative DMS across distinct growth conditions highlighted how functional contribution of different surfaces is highly context-dependent, varying alongside composition of targeted cell walls. These observations suggest that Tae1 engages with the intact cell wall network through a more distributed three-dimensional interaction interface than previously appreciated, providing an explanation for observed differences in antimicrobial potency across divergent Gram-negative competitors. Further binding studies of several Tae1 variants with their cognate immunity protein demonstrate that requirements to maintain protection from Tae activity may be a significant constraint on the mutational landscape of tae1 toxicity in the wild. In total, our work reveals that Tae diversification has likely been shaped by multiple independent pressures to maintain interactions with binding partners that vary across bacterial species and conditions. Antibacterial potency of type VI amidase effector toxins is dependent on substrate topology and cellular context.,Radkov A, Sapiro AL, Flores S, Henderson C, Saunders H, Kim R, Massa S, Thompson S, Mateusiak C, Biboy J, Zhao Z, Starita LM, Hatleberg WL, Vollmer W, Russell AB, Simorre JP, Anthony-Cahill S, Brzovic P, Hayes B, Chou S Elife. 2022 Jun 28;11:e79796. doi: 10.7554/eLife.79796. PMID:35762582[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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