7AE6

Crystal structure of di-AMPylated HEPN(R102A) toxin

7AE6 の概要

• エントリーDOI: 10.2210/pdb7ae6/pdb
• 関連するPDBエントリー: 7AE2
• 分子名称: HEPN toxin, ADENOSINE MONOPHOSPHATE, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: toxin-antitoxin system, mnt-hepn, ampylation, toxin
• 由来する生物種: Aphanizomenon flos-aquae 2012/KM1/D3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38270.50

構造登録者

Tamulaitiene, G.,Sasnauskas, G.,Songailiene, I.,Juozapaitis, J.,Siksnys, V. (登録日: 2020-09-17, 公開日: 2020-12-30, 最終更新日: 2024-11-06)

主引用文献

Songailiene, I.,Juozapaitis, J.,Tamulaitiene, G.,Ruksenaite, A.,Sulcius, S.,Sasnauskas, G.,Venclovas, C.,Siksnys, V.
HEPN-MNT Toxin-Antitoxin System: The HEPN Ribonuclease Is Neutralized by OligoAMPylation.
Mol.Cell, 80:955-970.e7, 2020

PubMed Abstract: Prokaryotic toxin-antitoxin (TA) systems are composed of a toxin capable of interfering with key cellular processes and its neutralizing antidote, the antitoxin. Here, we focus on the HEPN-MNT TA system encoded in the vicinity of a subtype I-D CRISPR-Cas system in the cyanobacterium Aphanizomenon flos-aquae. We show that HEPN acts as a toxic RNase, which cleaves off 4 nt from the 3' end in a subset of tRNAs, thereby interfering with translation. Surprisingly, we find that the MNT (minimal nucleotidyltransferase) antitoxin inhibits HEPN RNase through covalent di-AMPylation (diadenylylation) of a conserved tyrosine residue, Y109, in the active site loop. Furthermore, we present crystallographic snapshots of the di-AMPylation reaction at different stages that explain the mechanism of HEPN RNase inactivation. Finally, we propose that the HEPN-MNT system functions as a cellular ATP sensor that monitors ATP homeostasis and, at low ATP levels, releases active HEPN toxin.

PubMed: 33290744
DOI: 10.1016/j.molcel.2020.11.034

実験手法

X-RAY DIFFRACTION (1.65 Å)