7VKC

Molecular mechanism of toxin neutralization in the HipBST toxin-antitoxin system of Legionella pneumophila.

(2022) Nat Commun 13: 4333-4333

• PubMed: 35882877 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1038/s41467-022-32049-x
• Primary Citation of Related Structures:  
  7VKB, 7VKC, 7WCF


• PubMed Abstract: 
  

  Toxin-antitoxin (TA) systems are ubiquitous genetic modules in bacteria and archaea. Here, we perform structural and biochemical characterization of the Legionella pneumophila effector Lpg2370, demonstrating that it is a Ser/Thr kinase. Together with two upstream genes, lpg2370 constitutes the tripartite HipBST TA. Notably, the toxin Lpg2370 (HipT _Lp ) and the antitoxin Lpg2369 (HipS _Lp ) correspond to the C-terminus and N-terminus of HipA from HipBA TA, respectively. By determining crystal structures of autophosphorylated HipT _Lp , its complex with AMP-PNP, and the structure of HipT _Lp -HipS _Lp complex, we identify residues in HipT _Lp critical for ATP binding and those contributing to its interactions with HipS _Lp . Structural analysis reveals that HipS _Lp binding induces a loop-to-helix shift in the P-loop of HipT _Lp , leading to the blockage of ATP binding and inhibition of the kinase activity. These findings establish the L. pneumophila effector Lpg2370 as the HipBST TA toxin and elucidate the molecular basis for HipT neutralization in HipBST TA.

   View More

---

Organizational Affiliation: 

Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, 350117, Fuzhou, China.