8QNQ

Structure of the toxin-antitoxin NatRT complex from Pseudomonas aeruginosa. NatTE29D mutant

8QNQ の概要

• エントリーDOI: 10.2210/pdb8qnq/pdb
• 分子名称: Antitoxin Xre/MbcA/ParS-like toxin-binding domain-containing protein, RES domain-containing protein, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: res domain nadase nad+ pseudomonas aeruginosa, toxin
• 由来する生物種: Pseudomonas aeruginosa PAO1; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 116767.71

構造登録者

Dias Teixeira, R.,Hiller, S.,Jenal, U. (登録日: 2023-09-27, 公開日: 2024-10-02)

主引用文献

Santi, I.,Dias Teixeira, R.,Manfredi, P.,Hernandez Gonzalez, H.,Spiess, D.C.,Mas, G.,Klotz, A.,Kaczmarczyk, A.,Zamboni, N.,Hiller, S.,Jenal, U.
Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen.
Embo J., 2024

PubMed Abstract: Toxin-antitoxin (TA) systems are widespread in bacteria and implicated in genome stability, virulence, phage defense, and persistence. TA systems have diverse activities and cellular targets, but their physiological roles and regulatory mechanisms are often unclear. Here, we show that the NatR-NatT TA system, which is part of the core genome of the human pathogen Pseudomonas aeruginosa, generates drug-tolerant persisters by specifically depleting nicotinamide dinucleotides. While actively growing P. aeruginosa cells compensate for NatT-mediated NAD deficiency by inducing the NAD salvage pathway, NAD depletion generates drug-tolerant persisters under nutrient-limited conditions. Our structural and biochemical analyses propose a model for NatT toxin activation and autoregulation and indicate that NatT activity is subject to powerful metabolic feedback control by the NAD precursor nicotinamide. Based on the identification of natT gain-of-function alleles in patient isolates and on the observation that NatT increases P. aeruginosa virulence, we postulate that NatT modulates pathogen fitness during infections. These findings pave the way for detailed investigations into how a toxin-antitoxin system can promote pathogen persistence by disrupting essential metabolic pathways.

PubMed: 39322758
DOI: 10.1038/s44318-024-00248-5

実験手法

X-RAY DIFFRACTION (2.386 Å)