7WCF

Crystal structure of the kinase with AMP-PNP

7WCF の概要

• エントリーDOI: 10.2210/pdb7wcf/pdb
• 分子名称: HipA_C domain-containing protein, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: a toxin wildspread in the prokaryote cells., toxin
• 由来する生物種: Legionella pneumophila subsp. pneumophila str. Philadelphia 1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37714.60

構造登録者

Ouyang, S.Y.,Zhen, X. (登録日: 2021-12-20, 公開日: 2022-06-29, 最終更新日: 2024-11-13)

主引用文献

Zhen, X.,Wu, Y.,Ge, J.,Fu, J.,Ye, L.,Lin, N.,Huang, Z.,Liu, Z.,Luo, Z.Q.,Qiu, J.,Ouyang, S.
Molecular mechanism of toxin neutralization in the HipBST toxin-antitoxin system of Legionella pneumophila.
Nat Commun, 13:4333-4333, 2022

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) and the antitoxin Lpg2369 (HipS) correspond to the C-terminus and N-terminus of HipA from HipBA TA, respectively. By determining crystal structures of autophosphorylated HipT, its complex with AMP-PNP, and the structure of HipT-HipS complex, we identify residues in HipT critical for ATP binding and those contributing to its interactions with HipS. Structural analysis reveals that HipS binding induces a loop-to-helix shift in the P-loop of HipT, 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.

PubMed: 35882877
DOI: 10.1038/s41467-022-32049-x

実験手法

X-RAY DIFFRACTION (1.3636 Å)