7AER

Rebuilt and re-refined PDB entry 5yep: tri-AMPylated Shewanella oneidensis HEPN toxin in complex with MNT antitoxin

Summary for 7AER

• Entry DOI: 10.2210/pdb7aer/pdb
• Related: 7AE2 7AE6 7AE8 7AE9
• Descriptor: Toxin-antitoxin system antidote Mnt family, Toxin-antitoxin system toxin HepN family, ADENOSINE MONOPHOSPHATE (3 entities in total)
• Functional Keywords: toxin-antitoxin system, mnt-hepn, ampylation, toxin/antitoxin, toxin-antitoxin complex
• Biological source: Shewanella oneidensis (strain MR-1); More
• Total number of polymer chains: 4
• Total formula weight: 66566.24

Authors

Tamulaitiene, G.,Sasnauskas, G.,Songailiene, I.,Juozapaitis, J.,Siksnys, V. (deposition date: 2020-09-18, release date: 2020-12-30, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3 Å)