Significance and Impact The findings offer clues to the evolutionary origins of the potent toxins that enable bacterial pathogens to cause human diseases such as cholera and diphtheria Research Details ID: 933545
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Scientific AchievementResearchers solved the structure of a bacterial toxin (Tre1) bound to a neutralizing protein (Tri1), revealing two distinct mechanisms for how the toxin-producing bacteria avoid poisoning themselves. Significance and ImpactThe findings offer clues to the evolutionary origins of the potent toxins that enable bacterial pathogens to cause human diseases such as cholera and diphtheria.Research Details The Tre1–Tri1 complex revealed a protuberance from Tri1 (the "NTE") that blocks the Tre1 active site.Structural and genomic analyses suggested that Tri1 can also reverse Tre1's effects enzymatically.Subsequent bioassays showed that both mechanisms neutralize Tre1, but the enzymatic mode provides broader immunity to a variety of toxins.
Publication about this research: S.-Y. Ting, D.E. Bosch, S.M. Mangiameli, M.C. Radey, S. Huang, Y.-J. Park, K.A. Kelly, S.K. Filip, Y.A. Goo, J.K. Eng, M. Allaire, D. Veesler, P.A. Wiggins, S. Brook Peterson, and J.D. Mougous, Cell 175, 1380 (2018). Work was performed at Lawrence Berkeley National Laboratory, ALS Beamline 5.0.2. Operation of the ALS is supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences program.
Two-Pronged Defense against Bacterial Self-Intoxication
The active site (red) of the Tre1 toxin (yellow) is blocked by a protuberance from Tri1 (blue).
Comparison of the Tri1 structure (blue) to that of a similar protein (gray) capable of performing a reversal of the toxin’s enzymatic reaction.