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SJTU Team Jointly Discovered How Acetyl Translates Toxin–Antitoxin System

August 26, 2019      Author: Ou Hongyu

Recently, the well-known journal in molecular biology Nucleic Acids Research published the paper "Toxin-antitoxin operon kacAT of Klebsiella pneumoniae is regulated by conditional cooperativity via a W-shaped KacA-KacT complex". This research result is achieved by Ou Hongyu's team and He Xinyi's team from the National Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, SJTU and Gan Jianhua's team from the School of Life Sciences, Fudan University. It explored the bacterial type-II toxin-antitoxin system, and further elucidated the transcriptional regulation mechanism of the acetyltransferase GNA-RHH toxin-antitoxin system.

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Qian Hongliang and Yu Hao are co-first authors, and Professor Ou Hongyu, He Xinyi and Gan Jianhua are co-correspondence authors. The paper has attracted wide attention after publication and has been selected as the F1000Prime recommended paper. This research work is supported by the 973 Project and other foundations.

Abstract

Bacterial toxin-antitoxin pairs play important roles in bacterial multidrug tolerance. Gcn5-related N-acetyltransferase (GNAT) toxins inhibit translation by acetylation of aminoacyl-tRNAs and are counteracted by direct contacts with cognate ribbon-helix-helix (RHH) antitoxins. Our previous analysis showed that the GNAT toxin KacT and RHH antitoxin KacA of Klebsiella pneumoniae form a heterohexamer in solution and that the complex interacts with the cognate promoter DNA, resulting in negative autoregulation of kacAT transcription. Here, we present the crystal structure of DNA-bound KacAT complex at 2.2 Å resolution. The crystal structure revealed the formation of a unique heterohexamer, KacT-KacA2-KacA2-KacT. The direct interaction of KacA and KacT involves a unique W-shaped structure with the two KacT molecules at opposite ends. Inhibition of KacT is achieved by the binding of four KacA proteins that preclude the formation of an active KacT dimer. The kacAT operon is auto-regulated and we present an experimentally supported molecular model proposing that the KacT:KacA ratio controls kacAT transcription by conditional cooperativity. These results yield a profound understanding of how transcription GNAT-RHH pairs are regulated.

Paper link: https://academic.oup.com/nar/article/47/14/7690/5526705

 

Translated by Chen Qianqian       Reviewed by Wang Bingyu